TH17/IL-17 Research | Q=17

1. Arch Dermatol Res. 2018 Jul;310(5):383-390. doi: 10.1007/s00403-018-1823-y. Epub
2018 Mar 1.

IL-17 inhibition: is it the long-awaited savior for alopecia areata?

Ramot Y(1), Marzani B(2), Pinto D(2), Sorbellini E(3), Rinaldi F(3).

Author information:
(1)Department of Dermatology, Hadassah-Hebrew University Medical Center, PO Box
12000, 9112001, Jerusalem, Israel. yramot@gmail.com.
(2)Giuliani S.p.a., Milan, Italy.
(3)International Hair Research Foundation (IHRF), Milan, Italy.

Interleukin-17 (IL-17) has been implicated in the pathogenesis of a large number
of inflammatory and autoimmune conditions, including skin disorders such as
psoriasis. Recently, much data have accumulated on the possible role of IL-17 in
the pathogenesis of alopecia areata (AA). In this review, the available
information on the connection between AA and IL-17 is described. While IL-17
levels are consistently reported to be elevated in the serum and lesional skin
of AA patients, there is no clear connection between IL-17 levels and disease
severity or duration. Some evidence has suggested an association between IL-17
and an early-onset disease, although this awaits further confirmation. While
there is enough information to support clinical trials with IL-17-targeted
treatments, it is possible that they will be effective only in a subset of AA
patients. Further studies are warranted to better delineate the exact role of
IL-17 in AA pathogenesis.

DOI: 10.1007/s00403-018-1823-y
PMID: 29497840 [Indexed for MEDLINE]


2. Protein Pept Lett. 2015;22(7):570-8. doi: 10.2174/0929866522666150520145554.

An Overview of Interleukin-17A and Interleukin-17 Receptor A Structure,
Interaction and Signaling.

Krstic J, Obradovic H, Kukolj T, Mojsilovic S, Okic-Dordevic I, Bugarski D,
Santibanez JF(1).

Author information:
(1)Laboratory for Experimental Hematology and Stem cells. Institte for Medical
Research, University of Belgrade, Dr Subotica 4, 11129 Belgrade, Serbia.
jfsantibanez@imi.bg.ac.rs.

Interleukin-17A (IL-17A) and its receptor (IL-17RA) are prototype members of
IL-17 ligand/receptor family firstly identified in CD4+ T cells, which comprises
six ligands (IL-17A to IL- 17F) and five receptors (IL-17RA to IL-17RE). IL-17A
is predominantly secreted by T helper 17 (Th17) cells, and plays important roles
in the development of autoimmune and inflammatory diseases. IL-17RA is widely
expressed, and forms a complex with IL-17RC. Binding of IL-17A to this receptor
complex triggers the activation of several intracellular signaling pathways. In
this review, we aimed to summarize literature data about molecular features of
IL-17A and IL-17RA from gene to mature protein. We are also providing insight
into regulatory mechanisms, protein structural conformation, including
ligand-receptor interaction, and an overview of signaling pathways. Our aim was
to compile the data on molecular characteristics of IL-17A and IL-17RA which may
help in the understanding of their functions in health and disease.

DOI: 10.2174/0929866522666150520145554
PMID: 25990083 [Indexed for MEDLINE]


3. Autoimmun Rev. 2018 Dec;17(12):1176-1185. doi: 10.1016/j.autrev.2018.06.008.
Epub 2018 Oct 12.

IL-17 and IL-17-producing cells and liver diseases, with focus on autoimmune
liver diseases.

Beringer A(1), Miossec P(2).

Author information:
(1)Immunogenomics and Inflammation Research Unit EA4130, University of Lyon,
Lyon, France.
(2)Immunogenomics and Inflammation Research Unit EA4130, University of Lyon,
Lyon, France. Electronic address: pierre.miossec@univ-lyon1.fr.

The pro-inflammatory cytokine interleukin(IL)-17 and IL-17-producing cells are
important players in the pathogenesis of many autoimmune / inflammatory
diseases. More recently, they have been associated with liver diseases. This
review first describes the general knowledge on IL-17 and IL-17 producing cells.
The second part describes the in vitro and in vivo effects of IL-17 on liver
cells and the contribution of IL-17 producing cells to liver diseases. IL-17
induces immune cell infiltration and liver damage driving to hepatic
inflammation and fibrosis and contributes to autoimmune liver diseases. The
circulating levels of IL-17 and the frequency of IL-17-producing cells are
elevated in a variety of acute and chronic liver diseases. The last part focuses
on the effects of IL-17 deletion or neutralization in various murine models.
Some of these observed beneficial effects suggest that targeting the IL-17 axis
could be a new therapeutic strategy to prevent chronicity and progression of
various liver diseases.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.autrev.2018.06.008
PMID: 30321671 [Indexed for MEDLINE]


4. Zhonghua Kou Qiang Yi Xue Za Zhi. 2019 Jun 9;54(6):420-424. doi:
10.3760/cma.j.issn.1002-0098.2019.06.015.

[Research progress in secreting sytokines interferon-gamma and interleukin-17 of
T helper 1 and 17 cells on periodontitis].

[Article in Chinese; Abstract available in Chinese from the publisher]

Wang ZX(1), Chen LL.

Author information:
(1)Department of Periodontology, The Second Affiliated Hospital of Zhejiang
University of Medicine, Hangzhou 310009, China.

Periodontal disease (PD) is an infection-driven chronic inflammatory disease
characterized by the inflammation of tooth-supporting tissues and the
destruction of the associated alveolar bone. The immune response of the host to
periodontal pathogens infection determines the course and progress of the
disease. The effects of secreting cytokines interferon-gamma (IFN-γ) and
interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17 cells (Th17) on
the development of periodontitis has attracted much attention. IFN-γ is a
potential immune-modulatory cytokine and can mediate cellular immune responses
by activating various immune cells of the host such as macrophages. As one of
the most potential bone physiological regulation mediators, IL-17 is closely
related with alveolar bone resorption in periodontitis. This review elaborated
the relationship between IFN-γ and IL-17 in the progress of periodontitis,
providing new explanations into the development of periodontitis and alveolar
bone destruction caused by the host immune response.

Publisher: 牙周炎是以牙龈炎症和牙槽骨进行性破坏为特征的慢性感染性疾病，宿主感染微生物后的免疫炎症反应决定疾病的过程和进展。辅助性T细胞（T
helper，Th）1和Th17特征性分泌因子干扰素γ和白细胞介素17（interleukin-17，IL-17）在牙周炎发生发展的作用一直备受关注。干扰素γ是具有潜在免疫调节作用的细胞因子，可以激活机体多种免疫细胞（如巨噬细胞），介导细胞免疫应答。IL-17作为炎症因子中最具潜力的骨生理稳定调节介质，可直接影响牙槽骨吸收及牙周炎的发生发展。本文就Th
1和Th17特征性分泌因子干扰素γ及IL-17在牙周炎发生发展中的作用进行综述。.

DOI: 10.3760/cma.j.issn.1002-0098.2019.06.015
PMID: 31177684 [Indexed for MEDLINE]


5. Mediators Inflamm. 2015;2015:470458. doi: 10.1155/2015/470458. Epub 2015 Apr 27.

Interleukin-17 and its implication in the regulation of differentiation and
function of hematopoietic and mesenchymal stem cells.

Mojsilović S(1), Jauković A(1), Santibañez JF(1), Bugarski D(1).

Author information:
(1)Laboratory for Experimental Hematology and Stem Cells, Institute for Medical
Research, University of Belgrade, Dr. Subotića 4, P.O. Box 102, 11129 Belgrade,
Serbia.

Adult stem cells have a great potential applicability in regenerative medicine
and cell-based therapies. However, there are still many unresolved issues
concerning their biology, and the influence of the local microenvironment on
properties of stem cells has been increasingly recognized. Interleukin (IL-) 17,
as a cytokine implicated in many physiological and pathological processes,
should be taken into consideration as a part of a regulatory network governing
tissue-associated stem cells' fate. This review is focusing on the published
data on the effects of IL-17 on the properties and function of hematopoietic and
mesenchymal stem cells and trying to discuss that IL-17 achieves many of its
roles by acting on adult stem cells.

DOI: 10.1155/2015/470458
PMCID: PMC4427009
PMID: 25999667 [Indexed for MEDLINE]


6. Intern Med. 2017;56(13):1613-1619. doi: 10.2169/internalmedicine.56.8209. Epub
2017 Jul 1.

Cardiovascular and Metabolic Diseases Comorbid with Psoriasis: Beyond the Skin.

Furue M(1), Tsuji G(1), Chiba T(1), Kadono T(2).

Author information:
(1)Department of Dermatology, Kyushu University, Japan.
(2)Department of Dermatology, St. Marianna University School of Medicine, Japan.

A close association of systemic inflammation with cardiovascular diseases and
metabolic syndrome is recently a popular topic in medicine. Psoriasis is a
chronic inflammatory skin disease with a prevalence of approximately 0.1-0.5% in
Asians. It is characterized by widespread scaly erythematous macules that cause
significant physical and psychological burdens for the affected individuals. The
accelerated inflammation driven by the TNF-α/IL-23/IL-17A axis is now known to
be the major mechanism in the development of psoriasis. Psoriasis is not a mere
skin disease; it is significantly associated with cardiovascular diseases and
metabolic syndrome, which suggests that the chronic skin inflammation extends
the systemic inflammation beyond the skin. In this article, we review the
epidemiological and pathological aspects of psoriasis and its comorbidities.

DOI: 10.2169/internalmedicine.56.8209
PMCID: PMC5519460
PMID: 28674347 [Indexed for MEDLINE]


7. Eur J Clin Invest. 2018 Nov;48 Suppl 2:e12952. doi: 10.1111/eci.12952. Epub 2018
May 30.

Cytokine production by human neutrophils: Revisiting the "dark side of the
moon".

Tamassia N(1), Bianchetto-Aguilera F(1), Arruda-Silva F(1)(2), Gardiman E(1),
Gasperini S(1), Calzetti F(1), Cassatella MA(1).

Author information:
(1)Department of Medicine, Section of General Pathology, University of Verona,
Verona, Italy.
(2)CAPES Foundation, Ministry of Education of Brazil, Brasilia, Brazil.

Polymorphonuclear neutrophils are the most numerous leucocytes present in human
blood, and function as crucial players in innate immune responses. Neutrophils
are indispensable for the defence towards microbes, as they effectively counter
them by releasing toxic enzymes, by synthetizing reactive oxygen species and by
producing inflammatory mediators. Interestingly, recent findings have
highlighted an important role of neutrophils also as promoters of the resolution
of inflammation process, indicating that their biological functions go well
beyond simple pathogen killing. Consistently, data from the last decades have
highlighted that neutrophils may even contribute to the development of adaptive
immunity by performing previously unanticipated functions, including the
capacity to extend their survival, directly interact with other leucocytes or
cell types, and produce and release a variety of cytokines. In this article, we
will summarize the main features of, as well as emphasize some important
concepts on, the production of cytokines by human neutrophils.

© 2018 Stichting European Society for Clinical Investigation Journal Foundation.

DOI: 10.1111/eci.12952
PMID: 29772063 [Indexed for MEDLINE]


8. Arch Oral Biol. 2017 Nov;83:230-235. doi: 10.1016/j.archoralbio.2017.08.001.
Epub 2017 Aug 2.

Diabetes increases interleukin-17 levels in periapical, hepatic, and renal
tissues in rats.

Azuma MM(1), Gomes-Filho JE(2), Prieto AKC(2), Samuel RO(3), de Lima VMF(4),
Sumida DH(5), Ervolino E(5), Cintra LTA(6).

Author information:
(1)Department of Endodontics, São Paulo State University (Unesp), School of
Dentistry, Araçatuba, Rua José Bonifácio, 1193, Araçatuba, 16015-050, São Paulo,
Brazil; Department of Endodontics, Ingá University Center, UNINGÁ, Rod. PR 317,
6114- Parque Industrial 200, Maringá, Paraná, Brazil.
(2)Department of Endodontics, São Paulo State University (Unesp), School of
Dentistry, Araçatuba, Rua José Bonifácio, 1193, Araçatuba, 16015-050, São Paulo,
Brazil.
(3)Department of Endodontics, São Paulo State University (Unesp), School of
Dentistry, Araçatuba, Rua José Bonifácio, 1193, Araçatuba, 16015-050, São Paulo,
Brazil; Department of Clinical Dentistry, Dental School, UNIUBE, University of
Uberaba, Av. Nenê Sabino, 1801, Uberaba, 38055-500, Minas Gerais, Brazil.
(4)Department of Clinic and Surgery and Animal Reproduction, São Paulo State
University (Unesp), Araçatuba Veterinary Medicine, Rua Clóvis Pestana, 793,
Araçatuba, 16050-680, São Paulo, Brazil.
(5)Department of Basic Science, São Paulo State University (Unesp), School of
Dentistry, Araçatuba, São Paulo, Brazil.
(6)Department of Endodontics, São Paulo State University (Unesp), School of
Dentistry, Araçatuba, Rua José Bonifácio, 1193, Araçatuba, 16015-050, São Paulo,
Brazil. Electronic address: lucianocintra@foa.unesp.br.

OBJECTIVES: This study aimed to evaluate the association between endodontic
infection and diabetes on interleukin-17 levels in periapical, hepatic, and
renal tissues of rats.
DESIGN: Forty male rats were divided into groups: normoglycemic rats (N),
normoglycemic rats with apical periodontitis (N-AP), rats with experimental
diabetes (ED), and rats with experimental diabetes and apical periodontitis
(ED-AP). Diabetes was induced by intravenous streptozotocin injection, and blood
sugar levels were monitored to confirm disease development. Apical periodontitis
(AP) was induced by pulp exposure to the oral environment during 30days. After
30days, hepatic and renal tissues were obtained, and IL-17 levels were
quantified by ELISA. The right hemi-jaw was used to quantify IL-17 levels by
immunohistochemistry. The values obtained in parametric tests were tabulated and
analyzed statistically by analysis of variance (ANOVA) and Tukey tests, and the
values obtained for scores were statistically analyzed by using the
Kruskal-Wallis and Dun tests. The level of significance was set at 5%.
RESULTS: ED and ED-AP groups expressed significantly higher IL-17 levels in both
hepatic and renal tissues (p<0.05), compared to N and N-AP groups. Apical
periodontitis (AP) in ED-AP group was significantly more severe than that in
N-AP group (p<0.05). Furthermore, there was a significantly larger increase in
the IL-17 levels in ED-AP group compared to N group (p<0.05).
CONCLUSION: Our results indicate that diabetes increases IL-17 levels in hepatic
and renal tissues and also enhances IL-17 production in apical periodontitis
area of rats.

Copyright © 2017 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.archoralbio.2017.08.001
PMID: 28818706 [Indexed for MEDLINE]


9. Dermatology. 2017;233(6):413-418. doi: 10.1159/000479925. Epub 2017 Sep 28.

Is There a Relation between Vitamin D and Interleukin-17 in Vitiligo? A
Cross-Sectional Study.

Aly D(1), Mohammed F, Sayed K, Gawdat H, Mashaly H, Abdel Hay R, Elias T, Agaiby
M.

Author information:
(1)Department of Dermatology and Venereology, National Research Centre, Giza,
Egypt.

BACKGROUND: High interleukin (IL)-17 contributes to vitiligo pathogenesis.
Vitamin D has been assessed in vitiligo, with no reports targeting its relation
to IL-17.
OBJECTIVE: To evaluate a possible regulatory effect of vitamin D on IL-17 and
their relation to disease activity in vitiligo.
METHODS: This study included 30 vitiligo patients and 40 controls evaluated for
IL-17 and vitamin D serum levels by ELISA technique.
RESULTS: IL-17 was significantly higher (p = 0.001) whereas vitamin D was found
to be lower among the patients (p < 0.001). Multivariable regression was
performed to evaluate the relationship between IL-17 and vitamin D levels with
the demographic data on the patients, revealing a nonsignificant relationship (p
> 0.05). A significant positive correlation was noted between vitamin D levels
and disease duration.
CONCLUSION: Vitamin D represents a potential player in the pathogenesis of
vitiligo. Its possible regulatory relation to IL-17, together with its weight as
a screening tool in vitiligo, needs further evaluation.

© 2017 S. Karger AG, Basel.

DOI: 10.1159/000479925
PMID: 28954273 [Indexed for MEDLINE]


10. Cell Mol Immunol. 2016 Jul;13(4):418-31. doi: 10.1038/cmi.2015.105. Epub 2016
Mar 28.

The roles and functional mechanisms of interleukin-17 family cytokines in
mucosal immunity.

Song X(1)(2), He X(1), Li X(3), Qian Y(1)(2).

Author information:
(1)Shanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiao
Tong University School of Medicine, Shanghai 200001, China.
(2)Institute of Health Sciences, Shanghai Institutes for Biological Sciences,
Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine,
Shanghai 200025, China.
(3)Department of Immunology, Lerner Research Institute, Cleveland Clinic
Foundation, Cleveland, OH 44195, USA.

The mucosal immune system serves as our front-line defense against pathogens. It
also tightly maintains immune tolerance to self-symbiotic bacteria, which are
usually called commensals. Sensing both types of microorganisms is modulated by
signalling primarily through various pattern-recognition receptors (PRRs) on
barrier epithelial cells or immune cells. After sensing, proinflammatory
molecules such as cytokines are released by these cells to mediate either
defensive or tolerant responses. The interleukin-17 (IL-17) family members
belong to a newly characterized cytokine subset that is critical for the
maintenance of mucosal homeostasis. In this review, we will summarize recent
progress on the diverse functions and signals of this family of cytokines at
different mucosal edges.

DOI: 10.1038/cmi.2015.105
PMCID: PMC4947810
PMID: 27018218 [Indexed for MEDLINE]


11. J Neurol Sci. 2016 Sep 15;368:334-6. doi: 10.1016/j.jns.2016.07.052. Epub 2016
Jul 25.

Interleukin 17 alone is not a discriminant biomarker in early demyelinating
spectrum disorders.

Lebrun C(1), Cohen M(2), Pignolet B(3), Seitz-Polski B(4), Bucciarelli F(3),
Benzaken S(4), Kantarci O(5), Siva A(6), Okuda D(7), Pelletier D(8), Brassat
D(3); on behalf SFSEP, BIONAT Network; RISC.

Author information:
(1)Neurology, Hopital Pasteur2, Nice, France. Electronic address:
Lebrun.c@chu-nice.fr.
(2)Neurology, Hopital Pasteur2, Nice, France.
(3)Neurology, Hopital Purpan, Toulouse, France.
(4)Immunology, Hopital Archet, Nice, France.
(5)Mayo Clinic, Rochester, USA.
(6)Istanbul, Turkey.
(7)UTS, Dallas, USA.
(8)USC, Los Angeles, USA.

BACKGROUND: Radiologically isolated syndrome (RIS) is a sub clinical
demyelinating neurological disorder and to date no biomarker that triggers the
seminal event has been identified. As for multiple sclerosis (MS), disease
activity and clinical course are unpredictable. In MS, exploratory studies
reported increased IL-17 levels in CSF but results in detecting IL-17 in serum
at different stage of the disease are controversial.
OBJECTIVES: We investigate levels of IL-17 in serum and CSF in patients
diagnosed at different stages of demyelinating diseases (RIS, CIS, relapsing
remitting (RR) or active multiple sclerosis patients:AMS) as a marker of
inflammatory condition.
METHODS: 1417 sera has been tested for IL-17A (1177 from active MS, 80 RRMS, 35
RIS, 35 CIS, 10 IIH: idiopathic intracranial hypertension, and 80 controls) and
240 CSF from RIS, CIS, IIH and controls.
RESULTS: No difference has been found between RIS who early clinically converted
and CIS patients who rapidly evolve in McDonald or clinically definite MS, nor
active MS. No correlation was found with usual MRI or CSF criteria.
CONCLUSION: Our results do not confirm that IL-17 can be considerate as a
reliable marker of inflammation in the demyelinating spectrum disorders, either
in blood or CSF.

Copyright © 2016 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jns.2016.07.052
PMID: 27538659 [Indexed for MEDLINE]


12. Inflammation. 2015 Oct;38(5):1959-68. doi: 10.1007/s10753-015-0176-3.

Evaluation of Local and Systemic Levels of Interleukin-17, Interleukin-23, and
Myeloperoxidase in Response to Periodontal Therapy in Patients with Generalized
Aggressive Periodontitis.

Cifcibasi E(1), Koyuncuoglu C, Ciblak M, Badur S, Kasali K, Firatli E, Cintan S.

Author information:
(1)Department of Periodontology, Faculty of Dentistry, Istanbul University,
Capa, 34093, Istanbul, Turkey, ecifcibasi@hotmail.com.

We aimed to investigate serum and gingival crevicular fluid levels of
myeloperoxidase, interleukin-17, and interleukin-23 before and after nonsurgical
periodontal therapy in generalized aggressive periodontitis patients and compare
to those in healthy controls. Interleukin-17, interleukin-23, and
myeloperoxidase levels were measured by enzyme-linked immunosorbent assay in
gingival crevicular fluid and serum samples taken from 19 systemically healthy
generalized aggressive periodontitis patients and 22 healthy controls. In
addition, the levels of IL-17, IL-23, and myeloperoxidase were reassessed at
3 months after periodontal therapy in the generalized aggressive periodontitis
(GAP) group. Periodontal clinical parameters were also evaluated at baseline and
3 months post-therapy. The investigated molecule levels in serum decreased
significantly at 3 months as a result of the therapy (p = 0.014 for IL-17,
p = 0.000 for IL-23, and p = 0.001 for myeloperoxidase (MPO)). Significant
reductions were also observed in gingival crevicular fluid (GCF) IL-17, IL-23,
and MPO levels at 3 months after therapy (p = 0.000 for all molecules). However,
the GCF levels of IL-17, IL-23, and MPO in GAP patients were still higher than
those in the controls at 3 months (p = 0.001). A significant decrease in the
local and systemic levels of IL-17, IL-23, and MPO based on the therapy might
indicate the role of these mediators for tissue destruction in periodontal
tissues.

DOI: 10.1007/s10753-015-0176-3
PMID: 25939876 [Indexed for MEDLINE]


13. Biochem Biophys Res Commun. 2018 Dec 2;506(4):956-961. doi:
10.1016/j.bbrc.2018.10.129. Epub 2018 Nov 3.

Correlation of spatio-temporal characteristics of intestinal inflammation with
IL-17 in a rat model of hypoganglionosis.

Yu H(1), Cao NJ(2), Pan WK(1), Su L(3), Zhao YY(1), Tian DH(1), Xu WY(1), Gao
Y(4), Zheng BJ(5).

Author information:
(1)Department of Pediatric Surgery, The Second Affiliated Hospital, Xi'an
Jiaotong University, No 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
(2)Department of Infectious Diseases, Shaanxi Provincial People's Hospital, No
256, You Yi Xi Street, Xi'an, 710068, China.
(3)Department of Minimally Invasive Surgery, The People's Hospital of the
Ningxia Hui Autonomous Region, No 301, Zheng Yuan Bei Street, Yin Chuan, 750021,
Ningxia, China.
(4)Department of Pediatric Surgery, The Second Affiliated Hospital, Xi'an
Jiaotong University, No 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
Electronic address: ygao@mail.xjtu.edu.cn.
(5)Department of Pediatric Surgery, The Second Affiliated Hospital, Xi'an
Jiaotong University, No 157, Xi Wu Road, Xi'an, 710004, Shaanxi, China.
Electronic address: xazbj@163.com.

Interleukin 17 expression is increased in children with Hirschsprung disease,
which is characterized by intestinal inflammation. This study designed to
exploit the characteristics of intestinal inflammation and examine the
correlation of interleukin 17 in this process of hypoganglionosis model
established by benzalkonium chloride treatment. Colon sections from female rats
were treated with benzalkonium chloride to induce hypoganglionosis or with
saline alone as a sham control. C-reactive protein and tumor necrosis factor-ɑ
were used as markers of inflammation. Expression of C-reactive protein, tumor
necrosis factor-ɑ, and interleukin 17 was assessed in colon tissue and blood
serum on days 7, 14 and 21 after treatment. The correlation between C-reactive
protein, tumor necrosis factor-ɑ, and interleukin 17 expression was estimated
using the Spearman's rank-correlation coefficient. C-reactive protein, tumor
necrosis factor-ɑ, and interleukin 17 were strongly expressed in submucosa and
mucosa layers and serum from treated animals. The expression of C-reactive
protein, tumor necrosis factor-ɑ, and interleukin 17 maintained the highest
level at Day 21. Only C-reactive protein and tumor necrosis factor-ɑ expression
was increased in control animals and only on day 7. Spearman's rank correlation
coefficient was significant in C-reactive protein, tumor necrosis factor-ɑ, and
interleukin 17 at Day 7, 14 and 21. Concomitant upregulation of C-reactive
protein, tumor necrosis factor-ɑ, and interleukin 17 and significant positive
correlations between C-reactive protein, tumor necrosis factor-ɑ, and
interleukin 17 may imply that interleukin 17 is involved in spatio-temporal
inflammation induced by benzalkonium chloride.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.bbrc.2018.10.129
PMID: 30401564 [Indexed for MEDLINE]


14. Exp Neurol. 2018 Jan;299(Pt A):197-198. doi: 10.1016/j.expneurol.2017.11.004.

Animal models in autism research: The legacy of Paul H. Patterson.

Pardo CA(1), Meffert MK(2).

Author information:
(1)Department of Neurology & Division of Neuroimmunology and Neuroinfectious
Disorders. Electronic address: cpardov1@jhmi.edu.
(2)Department of Biological Chemistry; Solomon H. Snyder Department of
Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD21205,
USA. Electronic address: mkm@jhmi.edu.

DOI: 10.1016/j.expneurol.2017.11.004
PMCID: PMC5771678
PMID: 29223411 [Indexed for MEDLINE]


15. Mol Immunol. 2017 Oct;90:50-56. doi: 10.1016/j.molimm.2017.07.004. Epub 2017 Jul
10.

IL-17B: A new area of study in the IL-17 family.

Bie Q(1), Jin C(2), Zhang B(3), Dong H(4).

Author information:
(1)Department of Laboratory Medicine, Affiliated Hospital of Jining Medical
University, Jining, Shandong, PR China; Key Laboratory of Laboratory Medicine of
Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR
China.
(2)Department of Laboratory Medicine, Affiliated Hospital of Jining Medical
University, Jining, Shandong, PR China.
(3)Department of Laboratory Medicine, Affiliated Hospital of Jining Medical
University, Jining, Shandong, PR China; Key Laboratory of Laboratory Medicine of
Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, PR
China. Electronic address: zhb861109@163.com.
(4)Department of Laboratory Medicine, Affiliated Hospital of Jining Medical
University, Jining, Shandong, PR China. Electronic address:
donghaixin2011@126.com.

The interleukin (IL)-17 superfamily, a relatively new family of cytokines,
consists of six ligands (from IL-17A to IL-17F), which bind to five receptor
subtypes (from IL-17RA to IL-17RE) and induce downstream signaling. IL-17A, a
prototype member of this family, has been reported to be involved in the
pathogenesis of allergies, autoimmune diseases, allograft transplantations, and
malignancies. Unlike IL-17A, which is mainly produced by T helper 17 cells,
IL-17B is widely expressed in various tissues. Recently, the biological function
of IL-17B in diseases, particularly tumors, has attracted the attention of
researchers. We previously reported that the expression of IL-17RB increased in
gastric cancer tissues and demonstrated that IL-17B/IL-17RB signaling plays a
critical role in gastric tumor progression. However, studies on IL-17B are
scant. In this review, we detail the structural characteristics, expression
patterns, and biological activities of IL-17B and its potential role in the
pathogenesis of diseases.

Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.molimm.2017.07.004
PMID: 28704706 [Indexed for MEDLINE]


16. Autoimmunity. 2015 Jun;48(4):259-66. doi: 10.3109/08916934.2014.976630. Epub
2014 Oct 29.

Interleukin-17 is a critical target for the treatment of ankylosing enthesitis
and psoriasis-like dermatitis in mice.

Ebihara S(1), Date F, Dong Y, Ono M.

Author information:
(1)Department of Pathology, Tohoku University Graduate School of Medicine ,
Sendai , Japan and.

Ankylosis is a major pathological manifestation of spondyloarthropathy. The aim
of this study was to evaluate the effects of anti-IL-17 therapy on spontaneous
ankylosing enthesitis in mice. In this study, we used male DBA/1 mice as a
spontaneous ankylosis model. Serum IL-17 concentrations were determined using
enzyme-linked immunosorbent assay. Male DBA/1 mice from different litters were
mixed and caged together preceding the treatment at 10 weeks (wk) of age
(prophylaxis) or 21 wk of age (intervention). Treatment with anti-IL-17
antibodies or saline was initiated after caging in groups of mice and
administered weekly. The onset of tarsal ankylosis was assessed by ankle
swelling and histopathological examination. Pathological changes and mRNA
expression levels were assessed in joints and ears obtained at the experimental
end-point. We found that circulating IL-17 increased with the onset of ankylosis
in male DBA/1 mice, coinciding with the onset of dermatitis. The symptoms of
dermatitis corresponded to the pathological characteristics of psoriasis:
acanthosis with mild hyperkeratosis, scaling, epidermal microabscess formation
and augmented expression of K16, S100A8 and S100A9. Prophylactic administration
of anti-IL-17 antibodies significantly prevented the development of both
ankylosis and dermatitis in male DBA/1 mice caged together. On the other hand,
administration of anti-IL-17 antibodies after disease onset had a lesser but
significant effect on ankylosis progression but did not affect dermatitis
progression. In conclusion, IL-17 is a key mediator in the pathogenic process of
tarsal ankylosis and psoriasis-like dermatitis in male DBA/1 mice caged
together. Thus, IL-17 is a potential therapeutic target in ankylosing enthesitis
and psoriasis in humans.

DOI: 10.3109/08916934.2014.976630
PMID: 25352178 [Indexed for MEDLINE]


17. Mediators Inflamm. 2014;2014:463928. doi: 10.1155/2014/463928. Epub 2014 May 11.

Overexpression of interleukin-23 and interleukin-17 in the lesion of pemphigus
vulgaris: a preliminary study.

Xue J(1), Su W(2), Chen Z(2), Ke Y(2), Du X(2), Zhou Q(2).

Author information:
(1)Department of Hand and Plastic Surgery, The 2nd Affiliated Hospital & Yuying
Children's Hospital of Wenzhou Medical University, No. 109, Xueyuan West Road,
Wenzhou, Zhejiang 325027, China.
(2)Department of Dermatology, Wenzhou Hospital of Integrated Traditional Chinese
and Western Medicine, No. 75, Jinxiu Road, Wenzhou, Zhejiang 325027, China.

IL-23/IL-17 axis has been identified as major factor involved in the
pathogenesis of several autoimmune diseases; yet its pathogenetic role in
pemphigus vulgaris (PV) remains controversial. The aim of this research was to
investigate the potential role of IL-23/IL-17 axis in the immunopathogenesis of
PV, and correlation between IL-23+ cells and IL-17+ cells was also evaluated.
For this purpose, ten patients with PV, three patients with pemphigus foliaceus
(PF), and six healthy individuals were allocated to this research. The lesional
skin biopsy specimens were obtained before treatment. Then immunofluorescence
staining was performed to analyze the expression of IL-23 and IL-17 in the PV/PF
patients and the healthy individuals. The results showed that the numbers of
IL-23+ and IL-17+ cells were significantly higher in PV lesions, compared to PF
lesions and normal control skins, respectively (all P < 0.05). Moreover, the
correlation between IL-23+ cells and IL-17+ cells was significant (r = 0.7546; P
< 0.05). Taken together, our results provided evidence that the IL-23/IL-17 axis
may play a crucial role in the immunopathogenesis of PV and may serve as novel
therapeutic target for PV.

DOI: 10.1155/2014/463928
PMCID: PMC4037576
PMID: 24899786 [Indexed for MEDLINE]


18. Neuromuscul Disord. 2014 Nov;24(11):943-52. doi: 10.1016/j.nmd.2014.06.432. Epub
2014 Jun 20.

The role of interleukin-17 in immune-mediated inflammatory myopathies and
possible therapeutic implications.

Moran EM(1), Mastaglia FL(2).

Author information:
(1)Institute for Immunology & Infectious Diseases (IIID), Murdoch University,
Murdoch, WA, Australia. Electronic address: e.moran@iiid.com.au.
(2)Institute for Immunology & Infectious Diseases (IIID), Murdoch University,
Murdoch, WA, Australia; Western Australian Neuroscience Research Institute,
Centre for Neuromuscular & Neurological Disorders, University of Western
Australia, Australia.

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune
muscle disorders with distinct clinical and pathological features and underlying
immunopathogenic mechanisms. Traditionally, CD4(+) Th1 cells or CD8(+) cytotoxic
effector T cells and type I/II interferons have been primarily implicated in the
pathogenesis of the inflammatory myopathies. The presence of IL-17A producing
cells in the inflamed muscle tissue of myositis patients and the results of in
vitro studies suggest that IL-17A and the Th17 pathway may also have a key role
in these diseases. The contribution of IL-17A to other chronic inflammatory and
autoimmune diseases has been well established and clinical trials of IL-17A
inhibitors are now at an advanced stage. However the precise role of IL-17A in
the various forms of myositis and the potential for therapeutic targeting is
currently unknown and warrants further investigation.

Copyright © 2014 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.nmd.2014.06.432
PMID: 25052503 [Indexed for MEDLINE]


19. Nat Commun. 2013;4:1888. doi: 10.1038/ncomms2880.

Crystal structures of interleukin 17A and its complex with IL-17 receptor A.

Liu S(1), Song X, Chrunyk BA, Shanker S, Hoth LR, Marr ES, Griffor MC.

Author information:
(1)Structural Biology and Biophysics Group, Pfizer Groton Laboratories, Eastern
Point Road, Groton, Connecticut 06340, USA. shenping.liu@pfizer.com

The constituent polypeptides of the interleukin-17 family form six different
homodimeric cytokines (IL-17A-F) and the heterodimeric IL-17A/F. Their
interactions with IL-17 receptors A-E (IL-17RA-E) mediate host defenses while
also contributing to inflammatory and autoimmune responses. IL-17A and IL-17F
both preferentially engage a receptor complex containing one molecule of IL-17RA
and one molecule of IL-17RC. More generally, IL-17RA appears to be a shared
receptor that pairs with other members of its family to allow signaling of
different IL-17 cytokines. Here we report crystal structures of homodimeric
IL-17A and its complex with IL-17RA. Binding to IL-17RA at one side of the
IL-17A molecule induces a conformational change in the second, symmetry-related
receptor site of IL-17A. This change favors, and is sufficient to account for,
the selection of a different receptor polypeptide to complete the
cytokine-receptor complex. The structural results are supported by biophysical
studies with IL-17A variants produced by site-directed mutagenesis.

DOI: 10.1038/ncomms2880
PMID: 23695682 [Indexed for MEDLINE]


20. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019 Aug;31(8):983-988. doi:
10.3760/cma.j.issn.2095-4352.2019.08.014.

[Influence regulation of inflammatory immune response by interleukin-17
lipopolysaccharide-induced acute lung injury in mice].

[Article in Chinese]

Qin Y(1), Lao Q, Huang B, Li Y, Qin T, Huang Y.

Author information:
(1)Department of Critical Care Medicine, Guangxi Medical University Cancer
Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China. Corresponding
author: Lao Qifang, Email: qifanggl@126.com.

OBJECTIVE: To explore the immunomodulatory effects of interleukin-17 (IL-17) on
acute lung injury (ALI) induced by lipopolysaccharide (LPS).
METHODS: Thirty-six SPF-class C57BL/6 mice were divided into normal saline
control group (NS group) and LPS-induced ALI model group (LPS group, LPS 5 mg/kg
intratracheal drip) according to random number table method, with 18 mice in
each group. Six mice were sacrificed at 2, 6 and 24 hours after model
reproduction, and peripheral blood, lung and spleen tissues were harvested.
After staining with hematoxylin-eosin (HE), the pathological changes of lung
tissue were observed under microscope and the infiltration level of lymphocytes,
neutrophils and macrophages in the alveolar wall and tracheal wall were
detected. Immunohistochemistry was used to detect the protein expression of
IL-17 in alveolar wall and tracheal wall, and the correlation between IL-17
expression and lymphocytes, neutrophils and macrophages infiltration in alveolar
wall and tracheal wall were analyzed. The level of IL-17 in lung tissue
homogenate was determined by enzyme linked immunosorbent assay (ELISA). Flow
cytometry was used to detect the proportion of CD4+IL-17+ helper T cells (Th17
cells) in CD4+ T cells in peripheral blood, lung tissue and spleen tissue.
RESULTS: (1) Microscopy showed that the lung tissue structure of NS group was
basically normal at each time after model reproduction, and there was no obvious
inflammatory cell infiltration, while the lung tissue edema and inflammatory
reaction were gradually aggravated in the LPS group, and the lung injury score
was significantly higher than that in NS group at each time (2 hours: 4.47±1.42
vs. 1.10±0.55, 6 hours: 7.93±2.14 vs. 1.23±0.50, 24 hours: 12.67±2.67 vs.
1.20±0.61, all P < 0.01). (2) Immunohistochemistry showed that the protein
expression of IL-17 in alveolar wall and tracheal wall of LPS group increased
gradually with time, while that in NS group was negative or weak positive.
Quantitative analysis showed that the immunohistochemical staining score of
IL-17 protein in alveolar wall and tracheal wall of LPS group were higher than
those of NS group (alveolar wall: 2.70±1.40 vs. 0.90±0.37 at 2 hours, 5.10±1.76
vs. 1.17±0.59 at 6 hours, 9.67±1.32 vs. 1.10±0.45 at 24 hours; tracheal wall:
2.87±0.89 vs. 0.90±0.39 at 2 hours, 4.97±1.48 vs. 1.10±0.41 at 6 hours,
8.67±1.54 vs. 1.03±0.29 at 24 hours; all P < 0.05). (3) Correlation analysis
showed that the protein expression of IL-17 in alveolar wall and tracheal wall
were positively correlated with the degree of lymphocyte, neutrophil and
macrophage infiltration (alveolar wall: r value was 0.632, 0.550, 0.466;
tracheal wall: r value was 0.695, 0.662, 0.575, respectively; all P < 0.01). (4)
IL-17 content (μg/L) in lung tissue homogenate was significantly higher than
that in NS group at each time after model reproduction (2 hours: 1.37±0.14 vs.
1.01±0.18, 6 hours: 1.65±0.19 vs. 1.11±0.18, 24 hours: 1.92±0.36 vs. 1.17±0.24,
all P < 0.01). (5) The proportion of Th17 cells in the peripheral blood, lung
tissue and spleen tissue of the LPS group were higher than those of the NS group
at each time after model reproduction [peripheral blood: (2.62±0.62)% vs.
(1.42±0.40)% at 2 hours, (3.74±0.43)% vs. (1.27±0.32)% at 6 hours, (4.44±0.65)%
vs. (1.59±0.45)% at 24 hours; lung tissue: (2.32±0.44)% vs. (1.50±0.25)% at 2
hours, (3.66±0.36)% vs. (1.33±0.24)% at 6 hours, (4.60±0.54)% vs. (1.60±0.27)%
at 24 hours; spleen tissue: (1.49±0.36)% vs. (0.69±0.21)% at 2 hours,
(2.58±0.55)% vs. (0.59±0.18)% at 6 hours, (3.76±0.57)% vs. (0.65±0.26)% at 24
hours; all P < 0.01].
CONCLUSIONS: IL-17 is involved in the inflammatory immune regulation of ALI
mice.

DOI: 10.3760/cma.j.issn.2095-4352.2019.08.014
PMID: 31537224 [Indexed for MEDLINE]


21. J Periodontol. 2016 Nov;87(11):e183-e191. doi: 10.1902/jop.2016.150722. Epub
2016 Jul 23.

Effect of Curcumin on Systemic T Helper 17 Cell Response; Gingival Expressions
of Interleukin-17 and Retinoic Acid Receptor-Related Orphan Receptor γt; and
Alveolar Bone Loss in Experimental Periodontitis.

Bakır B(1), Yetkin Ay Z(1), Büyükbayram Hİ(2), Kumbul Doğuç D(2), Bayram D(3),
Candan IA(3), Uskun E(4).

Author information:
(1)Department of Periodontology, Faculty of Dentistry, Süleyman Demirel
University, Isparta, Turkey.
(2)Department of Biochemistry, Faculty of Medicine, Süleyman Demirel University.
(3)Department of Histology and Embryology, Faculty of Medicine, Süleyman Demirel
University.
(4)Department of Public Health, Faculty of Medicine, Süleyman Demirel
University.

BACKGROUND: Curcumin has anti-inflammatory and antioxidant effects and is
reported to have many biologic activities. The current study examines effect of
curcumin on: 1) systemic T helper 17 (Th17) cell response; 2) gingival
expressions of interleukin (IL)-17 and retinoic acid receptor-related orphan
receptor (ROR) γt; and 3) alveolar bone loss (ABL) in experimental
periodontitis.
METHODS: Thirty-eight male albino Wistar rats were divided into four groups: 1)
group 1 = periodontitis; 2) group 2 = periodontitis with curcumin treatment; 3)
group 3 = periodontally healthy with curcumin treatment; and 4) group 4 =
periodontally healthy. Curcumin was administered via oral gavage (30 mg/kg/d)
for 15 days. After sacrifice via exsanguination, the following serum levels were
determined using enzyme-linked immunosorbent assay: 1) IL-1β; 2) IL-6; 3)
IL-17A; 4) IL-23; and 5) transforming growth factor- β. Morphometric evaluation
of ABL was conducted and expression levels of IL-17 and RORγt in gingival
tissues were evaluated immunohistochemically.
RESULTS: Group 2 had significantly lower ABL than group 1 (P <0.0125). Highest
expression levels of IL-17 and RORγt were observed in group 1 and were
significantly higher than those in all other groups (P <0.0125). The only serum
biochemical parameter significantly different among groups was level of IL-23 (P
<0.05). Serum IL-23 levels were higher in groups 1 and 2 than groups 3 and 4 (P
<0.0125); however, they were not significantly different for groups 1 and 2 (P
>0.0125).
CONCLUSION: Curcumin seems to be a promising host modulatory agent in
periodontal disease pathogenesis regarding IL-17/IL-23 axis, with a decreasing
effect on ABL and gingival expressions of IL-17 and RORγt.

DOI: 10.1902/jop.2016.150722
PMID: 27452394 [Indexed for MEDLINE]


22. Eur Respir J. 2016 Mar;47(3):990-3. doi: 10.1183/13993003.00446-2015. Epub 2016
Jan 7.

Deficient interleukin-17 production in response to Mycobacterium abscessus in
cystic fibrosis.

Becker KL(1), van Ingen J(2), Ten Oever J(1), Merkus PJ(3), Ferwerda G(4), Netea
MG(1), Magis-Escurra C(5), Reijers MH(5), van de Veerdonk FL(6).

Author information:
(1)Dept of Internal Medicine, Radboud University Medical Centre, Nijmegen, The
Netherlands.
(2)Dept of Medical Microbiology, Radboud University Medical Centre, Nijmegen,
The Netherlands.
(3)Dept of Pediatrics, Division of Respiratory Medicine, Radboud University
Medical Centre, Nijmegen, The Netherlands.
(4)Dept of Pediatrics, Laboratory of Pediatric Infectious Diseases, Radboud
University Medical Centre, Nijmegen, The Netherlands.
(5)Dept of Pulmonology, Radboud University Medical Centre, Nijmegen, The
Netherlands.
(6)Dept of Internal Medicine, Radboud University Medical Centre, Nijmegen, The
Netherlands Frank.vandeVeerdonk@radboudumc.nl.

DOI: 10.1183/13993003.00446-2015
PMID: 26743483 [Indexed for MEDLINE]


23. Int Rev Immunol. 2013 Oct-Dec;32(5-6):544-55. doi: 10.3109/08830185.2013.821118.
Epub 2013 Jul 25.

Inhibition of IL-17 as a pharmacological approach for IBD.

Fitzpatrick LR(1).

Author information:
(1)Department of Pharmacology, Penn State College of Medicine , Hummelstown,
Pennsylvania , USA.

Several experimental approaches have been utilized, in order to critically
examine the roles of IL-17 family members in intestinal inflammation. These
approaches have included: (1) the use of IL-17A and IL-17F-deficient mice, (2)
specific antibodies directed against IL-17, (3) an IL-17 vaccine, (4) methods to
block the IL-17 receptor and (5) small-molecule inhibitors of IL-17. Previous
studies found somewhat conflicting results in preclinical models of Inflammatory
Bowel Disease (IBD), using specific strains of IL-17-deficient mice. This paper
will review the preclinical results using various pharmacological approaches
[specific IL-17 antibodies, an IL-17 receptor fusion protein, IL-12/IL-23 p40
subunit and IL-17 vaccine approaches, as well as a small molecule inhibitor
(Vidofludimus)] to inhibit IL-17 in animal models of IBD. Recent clinical
results in patients with IBD will also be discussed for Secukinumab (an IL-17A
antibody), Brodalumab (an IL-17 receptor antibody) and two small-molecule drugs
(Vidofludimus and Tofacitinib), which inhibit IL-17 as part of their overall
pharmacological profiles. This review paper will also discuss some
pharmacological lessons learned from the preclinical and clinical studies with
anti-IL-17 drugs, as related to drug pharmacodynamics, IL-17 receptor subtypes
and other pertinent factors. Finally, future pharmacological approaches of
interest will be discussed, such as: (1) Retinoic acid receptor-related orphan
nuclear receptor gamma t (Rorγt) antagonists, (2) Retinoic acid receptor alpha
(RARα) antagonists, (3) Pim-1 kinase inhibitors and (4) Dual small-molecule
inhibitors of NF-κB and STAT3, like synthetic triterpenoids.

DOI: 10.3109/08830185.2013.821118
PMID: 23886112 [Indexed for MEDLINE]


24. Mucosal Immunol. 2018 May;11(3):581-589. doi: 10.1038/mi.2017.97. Epub 2017 Nov
29.

Mucocutaneous IL-17 immunity in mice and humans: host defense vs. excessive
inflammation.

Li J(1), Casanova JL(1)(2)(3)(4)(5), Puel A(1)(2)(3).

Author information:
(1)St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller
Branch, The Rockefeller University, New York, NY, USA.
(2)Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM
U1163, Paris, France.
(3)Paris Descartes University, Imagine Institute, Paris, France.
(4)Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children,
Paris, France.
(5)Howard Hughes Medical Institute, New York, NY, USA.

Interleukin (IL)-17A is a pro-inflammatory cytokine in mice and humans. It is
recognized as a key factor for the protection of mice against various pathogens,
but it also underlies pathogenic inflammatory responses in numerous mouse
models. The inborn errors of IL-17A- and IL-17F-mediated immunity identified in
humans in the last decade have revealed that IL-17A and IL-17F are key players
in mucocutaneous immunity to Candida albicans, and, to a lesser extent,
Staphylococcus aureus. By contrast, there is currently no genetic evidence for a
causal link between excess of IL-17 and autoimmunity, autoinflammation, or
allergy in humans. We discuss here the physiological and pathological roles of
mouse and human IL-17A and IL-17F in host defense and excessive inflammation. We
highlight recent advances in our understanding of the consequences of deficient
or excessive IL-17 immunity at various mucocutaneous sites, including the oral
cavity, skin, intestine, lungs, and vagina.

DOI: 10.1038/mi.2017.97
PMCID: PMC5975098
PMID: 29186107 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of interest The authors have no
conflict of interest to declare.


25. Mediators Inflamm. 2016;2016:7179214. doi: 10.1155/2016/7179214. Epub 2016 Apr
21.

Th17 Cytokines and Barrier Functions.

Wang G(1), Bao M(2), Zhang X(3), Majtan J(4), Chen K(5).

Author information:
(1)Institute of Respiratory Diseases, Xinqiao Hospital, Chongqing, China.
(2)MedImmune LLC, 1 MedImmune Way, Gaithersburg, MD 20878, USA.
(3)Lester and Sue Smith Breast Center, Department of Molecular and Cellular
Biology, Baylor College of Medicine, Houston, TX 77030, USA.
(4)Institute of Molecular Biology, Slovak Academy of Sciences, Dubravska Cesta
21, 845 51 Bratislava, Slovakia.
(5)Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh Medical
Center, PA 15224, USA.

DOI: 10.1155/2016/7179214
PMCID: PMC4856936
PMID: 27199508 [Indexed for MEDLINE]


26. J Immunol. 2018 Dec 1;201(11):3153-3159. doi: 10.4049/jimmunol.1801042.

IL-17 in Renal Immunity and Autoimmunity.

Biswas PS(1).

Author information:
(1)Division of Rheumatology and Clinical Immunology, University of Pittsburgh,
Pittsburgh, PA 15261 psb13@pitt.edu.

The kidney is an organ particularly susceptible to damage caused by infections
and autoimmune conditions. Renal inflammation confers protection against
microbial infections. However, if unchecked, unresolved inflammation may lead to
kidney damage. Although proinflammatory cytokine IL-17 is required for immunity
against extracellular pathogens, dysregulated IL-17 response is also linked to
autoimmunity. In this review, we will discuss the current knowledge of IL-17
activity in the kidney in context to renal immunity and autoimmunity and raise
the intriguing question to what extent neutralization of IL-17 is beneficial or
harmful to renal inflammation.

Copyright © 2018 by The American Association of Immunologists, Inc.

DOI: 10.4049/jimmunol.1801042
PMCID: PMC6524787
PMID: 30455371 [Indexed for MEDLINE]


27. J Periodontol. 2016 May;87(5):591-600. doi: 10.1902/jop.2015.150390. Epub 2015
Dec 14.

The Influences of Periodontal Status and Periodontal Pathogen Quantity on
Salivary 8-Hydroxydeoxyguanosine and Interleukin-17 Levels.

Yang X(1), Li C(1), Pan Y(1).

Author information:
(1)Department of Periodontics and Oral Biology, School of Stomatology, China
Medical University, Shenyang, Liaoning, China.

BACKGROUND: Periodontitis is a biofilm-initiated disease that is characterized
by elevated inflammatory status. 8-Hydroxydeoxyguanosine (8-OHdG) and
interleukin (IL)-17 are highly associated with inflammation and bone resorption
and therefore are regarded as potential biomarkers for periodontitis. In this
study, the associations between salivary 8-OHdG and IL-17 levels and clinical
and microbial parameters before and after non-surgical treatment are
investigated.
METHODS: Forty-five patients with chronic periodontitis (CP) and 47
periodontally healthy volunteers were recruited for the study. Clinical
parameters, including the probing depth (PD), clinical attachment level (CAL),
sulcular bleeding index, and simplified oral hygiene index (OHI-S), were
examined for each participant. Microbial parameters including the quantities of
Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in the
subgingival plaque and saliva were determined by real-time polymerase chain
reaction at baseline and 1 and 3 months after the non-surgical treatment.
Salivary 8-OHdG and IL-17 levels were detected by enzyme-linked immunosorbent
assays.
RESULTS: Compared with healthy volunteers, CP group patients had significantly
higher salivary 8-OHdG and IL-17 levels at baseline. Baseline salivary 8-OHdG
and IL-17 levels were positively correlated with all clinical parameters as well
as the quantities of T. forsythia and T. denticola. After non-surgical
treatment, baseline levels of salivary 8-OHdG and IL-17 were reduced
significantly at both the 1- and 3-month follow-ups. The hierarchical linear
model revealed that variations in the PD, CAL, and OHI-S had significant
positive effects on variation in the salivary 8-OHdG level. However, variations
in the PD; quantity of T. forsythia in the subgingival plaque; and quantities of
P. gingivalis, T. forsythia, and T. denticola in saliva were associated
significantly with variation in the salivary IL-17 levels.
CONCLUSIONS: There was a strong association between salivary 8-OHdG and IL-17
levels and periodontitis. Variation in the salivary 8-OHdG level was correlated
with variations in the clinical parameters, whereas variation in the IL-17 level
was correlated with variation in the microbial parameters.

DOI: 10.1902/jop.2015.150390
PMID: 26654345 [Indexed for MEDLINE]


28. Clin Infect Dis. 2016 Apr 1;62(7):951-3. doi: 10.1093/cid/ciw020. Epub 2016 Jan
19.

Ruxolitinib Induces Interleukin 17 and Ameliorates Chronic Mucocutaneous
Candidiasis Caused by STAT1 Gain-of-Function Mutation.

Mössner R(1), Diering N(1), Bader O(2), Forkel S(1), Overbeck T(3), Gross U(2),
Grimbacher B(4), Schön MP(1), Buhl T(1).

Author information:
(1)Department of Dermatology, Venereology and Allergology.
(2)Institute of Medical Microbiology.
(3)Department of Hematology and Oncology, University Medical Center Göttingen.
(4)Center for Chronic Immunodeficiency, University Medical Center Freiburg,
Germany Institute of Immunity and Transplantation, University College London,
United Kingdom.

DOI: 10.1093/cid/ciw020
PMID: 26787170 [Indexed for MEDLINE]


29. Acta Pharm. 2019 Dec 1;69(4):511-523. doi: 10.2478/acph-2019-0047.

A modern approach to the treatment of plaque psoriasis.

Drvar DL(1), Vlahinić T(2), Maleš Ž(3), Turčić P(4), Čeović R(1).

Author information:
(1)Department of Dermatology and Venereology, University Hospital Centre Zagreb,
School of Medicine, University of Zagreb, HR-10000 Zagreb, Croatia.
(2)Department of Infectious Diseases and Dermatovenereology, Dubrovnik General
Hospital, HR-20000 Dubrovnik, Croatia.
(3)University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of
Pharmaceutical Botany, HR-10000 Zagreb, Croatia.
(4)University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of
Pharmacology, HR-10000 Zagreb, Croatia.

Psoriasis is a common chronic inflammatory skin disease which affects 0.5-1 % of
children and 2-3 % of the adult population. In Croatia, 1.6 % of the population
suffer from psoriasis. Distribution of the disease is bimodal, with the first
peak at the age of 20-30, and the second at the age of 50-60. The
etiopathogenesis of the disease is multifactorial, the key factors being genetic
predisposition combined with immunological disorders, environmental factors and
skin barrier damage. There are several clinical variants of the disease. The
main signalling pathways in psoriasis include TNF-α, IL-23 and IL-17. Topical
agents are used for the treatment of the mild form, and the systemic
conventional therapy is used for the treatment of moderate to severe forms of
the disease. In cases where's no response, or intolerance or contraindications
are present, new targeted medications are to be administered. Development in the
field of immunogenetics of psoriasis leads to personalized medicine.

DOI: 10.2478/acph-2019-0047
PMID: 31639088 [Indexed for MEDLINE]


30. Acta Neurol Scand. 2011 Oct;124(4):293; author reply 294. doi:
10.1111/j.1600-0404.2011.01501.x.

Interleukin-17 and -23 levels in amyotrophic lateral sclerosis.

Kawabe K, Yoshii Y, Ikeda K, Iwasaki Y.

Comment on
    Acta Neurol Scand. 2010 Dec;122(6):425-9.

DOI: 10.1111/j.1600-0404.2011.01501.x
PMID: 21943036 [Indexed for MEDLINE]


31. Curr Allergy Asthma Rep. 2017 May;17(5):31. doi: 10.1007/s11882-017-0699-9.

Chronic Candidiasis in Children.

Green L(1), Dolen WK(2).

Author information:
(1)From the Department of Pediatrics, Allergy-Immunology and Pediatric
Rheumatology Division, Medical College of Georgia at Augusta University, 1120
15th Street, Augusta, GA, 30912, USA.
(2)From the Department of Pediatrics, Allergy-Immunology and Pediatric
Rheumatology Division, Medical College of Georgia at Augusta University, 1120
15th Street, Augusta, GA, 30912, USA. bdolen@augusta.edu.

PURPOSE OF REVIEW: Healthy children may develop candidal infections as the
result of exposure to antibiotics or corticosteroids, but chronic candidiasis in
children after the newborn period is unusual. Chronic mucocutaneous candidiasis
(CMC) refers to a group of conditions characterized by recurrent or persistent
infections with Candida species, particularly Candida albicans. CMC is a
phenotype observed in a spectrum of immunologic disorders, some with
endocrinologic and autoimmune features.
RECENT FINDINGS: CMC can arise secondary to inherited or acquired T cell
deficiencies, but in children is largely due to inborn errors impairing the
dectin pathway and IL-17 immunity. We review the current understanding of the
pathogenesis of chronic mucocutaneous candidiasis and discuss the immunologic
pathways by which the immune system handles Candida. We highlight the historical
and recent knowledge of CMC in children, emphasizing recent insights into basic
science aspects of the dectin pathway, IL-17 signaling, consequences of AIRE
gene defects, and clinical aspects of inheritance, and features that distinguish
the different syndromes. The clinical phenotype of CMC has many underlying
genetic causes. Genetic testing is required for definitive diagnosis.

DOI: 10.1007/s11882-017-0699-9
PMID: 28429308 [Indexed for MEDLINE]


32. Cell Immunol. 2018 Feb;324:8-13. doi: 10.1016/j.cellimm.2017.11.005. Epub 2017
Nov 15.

Th17 pathway in recent-onset autoimmune diabetes.

Fores JP(1), Crisostomo LG(1), Orii NM(2), Santos AS(3), Fukui RT(4), Matioli
SR(5), de Moraes Vasconcelos D(6), Silva MERD(7).

Author information:
(1)Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das
Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo
455, São Paulo 01246903, Brazil.
(2)Laboratório de Investigação em Dermatologia e Imunodeficiências (LIM - 56),
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av
Dr Arnaldo 455, São Paulo 01246903, Brazil. Electronic address: nory@usp.br.
(3)Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das
Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo
455, São Paulo 01246903, Brazil. Electronic address: aritania@usp.br.
(4)Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das
Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo
455, São Paulo 01246903, Brazil. Electronic address: rfukui@usp.br.
(5)Departamento de Genética e Biologia Evolutiva - Instituto de Biociências da
Universidade de São Paulo, Rua do Matão, 277, 05422-970 São Paulo, Brazil.
Electronic address: srmatiol@ib.usp.br.
(6)Laboratório de Investigação em Dermatologia e Imunodeficiências (LIM - 56),
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av
Dr Arnaldo 455, São Paulo 01246903, Brazil. Electronic address:
dewton.vasconcelos@hc.fm.usp.br.
(7)Laboratório de Carboidratos e Radioimunoensaio (LIM 18), Hospital das
Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo
455, São Paulo 01246903, Brazil. Electronic address: mbeth@usp.br.

AIMS: Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper
17 cells are potent, highly inflammatory cells that produce interleukin 17A
(IL-17A), considered a mediator of various immune disorders. However, their role
in Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated.
METHODS: The expression of IL-17 Receptor A (IL-17RA) in peripheral T
lymphocytes and IL-17A serum levels in recent-onset patients with T1D were
compared with healthy controls. IL-17A gene variants were evaluated in a greater
cohort.
RESULTS: Patients with recent-onset T1D (less than 6 months of diagnosis)
exhibited lower expression of IL-17RA in CD3+ T (% of cells = 31.3% × 43.6%;
p = .041) and CD4+ T cells (11.1% × 25.2%; p = .0019) and lower number of
IL-17RA in CD4+ T cells (MFI = 1.16 × 4.56; p = .03) than controls. IL-17RA
expression in CD8+ T cells and IL-17A serum levels were similar in both groups.
The coding regions and boundary intron sequences of IL17A were sequenced.
Seventeen allelic variants, including three novel variants in exon 3 (3'UTR n)
were identified, but no one was associated with T1D susceptibility, as well as
the resulting haplotypes and diplotypes. The expression of IL-17RA was not
correlated with metabolic variables (glucose and HbA1c levels) or pancreatic
autoantibodies titers.
CONCLUSIONS: The lower expression of IL-17RA in CD3+ and CD4+ T cells suggests a
reduced effect of IL-17A in immune response of recent-onset T1D patients, at
least at peripheral tissues. IL-17A allelic variants were not related with T1D
susceptibility.

Copyright © 2017 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.cellimm.2017.11.005
PMID: 29183760 [Indexed for MEDLINE]


33. Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2652-2661. doi:
10.1073/pnas.1818812116. Epub 2019 Jan 28.

Mutual interplay between IL-17-producing γδT cells and microbiota orchestrates
oral mucosal homeostasis.

Wilharm A(1), Tabib Y(2), Nassar M(2), Reinhardt A(1), Mizraji G(3), Sandrock
I(1), Heyman O(3), Barros-Martins J(1), Aizenbud Y(2), Khalaileh A(4),
Eli-Berchoer L(2), Elinav E(5), Wilensky A(3), Förster R(1), Bercovier H(6),
Prinz I(7), Hovav AH(8).

Author information:
(1)Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
(2)Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University,
9190501 Jerusalem, Israel.
(3)Department of Periodontology, Faculty of Dental Medicine, Hadassah Medical
Center, 12000 Jerusalem, Israel.
(4)General Surgery Department, Hadassah Hebrew University Medical Center, 12000
Jerusalem, Israel.
(5)Department of Immunology, Weizmann Institute of Science, 7610001 Rehovot,
Israel.
(6)Department of Microbiology and Molecular Genetics, Faculty of Medicine,
Hebrew University, 9190501 Jerusalem, Israel.
(7)Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany;
prinz.immo@mh-hannover.de avihaih@ekmd.huji.ac.il.
(8)Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University,
9190501 Jerusalem, Israel; prinz.immo@mh-hannover.de avihaih@ekmd.huji.ac.il.

γδT cells are a major component of epithelial tissues and play a role in tissue
homeostasis and host defense. γδT cells also reside in the gingiva, an oral
tissue covered with specialized epithelium that continuously monitors the
challenging dental biofilm. Whereas most research on intraepithelial γδT cells
focuses on the skin and intestine epithelia, our knowledge on these cells in the
gingiva is still incomplete. In this study, we demonstrate that even though the
gingiva develops after birth, the majority of gingival γδT cells are fetal
thymus-derived Vγ6+ cells, and to a lesser extent Vγ1+ and Vγ4+ cells.
Furthermore, we show that γδT cells are motile and locate preferentially in the
epithelium adjacent to the biofilm. Vγ6+ cells represent the major source of
IL-17-producing cells in the gingiva. Chimeric mice and parabiosis experiments
indicated that the main fraction of gingival γδT cells is radioresistant and
tissue-resident, persisting locally independent of circulating γδT cells.
Notably, gingival γδT cell homeostasis is regulated by the microbiota as the
ratio of Vγ6+ and Vγ4+ cells was reversed in germ-free mice, and their
activation state was decreased. As a consequence, conditional ablation of γδT
cells results in elevated gingival inflammation and subsequent alterations of
oral microbial diversity. Taken together, these findings suggest that oral
mucosal homeostasis is shaped by reciprocal interplays between γδT cells and
local microbiota.

DOI: 10.1073/pnas.1818812116
PMCID: PMC6377488
PMID: 30692259 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.


34. J Dermatol. 2012 Mar;39(3):219-24. doi: 10.1111/j.1346-8138.2011.01458.x.

Critical role of the interleukin-23/T-helper 17 cell axis in the pathogenesis of
psoriasis.

Nakajima K(1).

Author information:
(1)Department of Dermatology, Kochi Medical School, Kochi University, Kochi,
Japan. nakajimk@kochi-u.ac.jp

Psoriasis is an inflammatory disease with dynamic interactions between the
immune system and the skin. Recent studies have demonstrated that the
interleukin (IL)-23/T-helper (Th)17 cell axis plays an important role in the
pathogenesis of psoriasis. Here, the biology and function of Th17 cells as well
as the crucial role of IL-23 in the context of the Th17 cell-dependent chronic
inflammation in psoriatic skins are reviewed. Recent study about the role of the
IL-23/Th17 axis in the pathogenesis of psoriasis-like lesions in K5.Stat3C
transgenic mice is also discussed. This model mouse for psoriasis not only
verifies the therapeutic efficacies of biologics that specifically target the
IL-23/Th17 axis, but also clarifies the pathogenesis of psoriasis.

© 2012 Japanese Dermatological Association.

DOI: 10.1111/j.1346-8138.2011.01458.x
PMID: 22352845 [Indexed for MEDLINE]


35. J Am Acad Dermatol. 2013 Nov;69(5):840-842. doi: 10.1016/j.jaad.2013.07.026.

Assessment of interleukin-17 and vitamin D serum levels in psoriatic patients.

El-Moaty Zaher HA(1), El-Komy MHM(2), Hegazy RA(1), Mohamed El Khashab HA(3),
Ahmed HH(4).

Author information:
(1)Department of Dermatology, Faculty of Medicine, Cairo University, Cairo,
Egypt.
(2)Department of Dermatology, Faculty of Medicine, Cairo University, Cairo,
Egypt. Electronic address: komy_m@yahoo.com.
(3)Department of Dermatology, National Research Centre, Cairo, Egypt.
(4)Department of Biochemistry, National Research Centre, Cairo, Egypt.

DOI: 10.1016/j.jaad.2013.07.026
PMID: 24124829 [Indexed for MEDLINE]


36. Trends Pharmacol Sci. 2009 Feb;30(2):95-103. doi: 10.1016/j.tips.2008.11.004.
Epub 2009 Jan 21.

Interleukin-17 as a drug target in human disease.

Ivanov S(1), Lindén A.

Author information:
(1)AstraZeneca R&D Lund, S-221 87 Lund, Sweden.

Interleukin (IL)-17 (now synonymous with IL-17A) is an archetype molecule for an
entire family of IL-17 cytokines. Currently believed to be produced mainly by a
specific subset of CD4 cells, named Th-17 cells, IL-17 is functionally located
at the interface of innate and acquired immunity. Specifically, it induces the
release of chemokines and growth factors from mesenchymal cells and is now
emerging as an important local orchestrator of neutrophil accumulation in
several mammalian organs. Furthermore, there is growing evidence that targeting
IL-17 signaling might prove useful in a variety of diseases including asthma,
Crohn's disease, multiple sclerosis, psoriatric disease and rheumatoid
arthritis. Here, we summarize the key aspects of the biology of IL-17 in mammals
and scrutinize the potential pharmacological use of targeting IL-17 in humans.

DOI: 10.1016/j.tips.2008.11.004
PMID: 19162337 [Indexed for MEDLINE]


37. Acta Neurol Scand. 2010 Dec;122(6):425-9. doi: 10.1111/j.1600-0404.2010.01333.x.

Interleukin-17 and interleukin-23 are elevated in serum and cerebrospinal fluid
of patients with ALS: a reflection of Th17 cells activation?

Rentzos M(1), Rombos A, Nikolaou C, Zoga M, Zouvelou V, Dimitrakopoulos A,
Alexakis T, Tsoutsou A, Samakovli A, Michalopoulou M, Evdokimidis J.

Author information:
(1)Department of Neurology, Aeginition Hospital, Athens National University,
School of Medicine, Athens, Greece. mrentzos@med.uoa.gr

Comment in
    Acta Neurol Scand. 2011 Oct;124(4):293; author reply 294.

BACKGROUND: There is evidence that immunological factors may involved in
pathogenetic mechanisms of amyotrophic lateral sclerosis (ALS). Th17 cells are
characterized by predominant production of IL-17 and are suggested to be crucial
in destructive autoimmunity. Interleukin-23 (IL-23) appears to play a supporting
role in the continued stimulation and survival of Th17.
PATIENTS AND METHODS: We measured by enzyme-like immunosorbent assay (ELISA)
serum and cerebrospinal fluid (CSF) levels of IL-17 and IL-23 in 22 patients
with ALS and 19 patients with other non-inflammatory neurological disorders
(NIND) studied as a control group. IL-17 and IL-23 serum and CSF levels were
also correlated with duration of the disease, the disability level and the
clinical subtype of the disease onset in patients with ALS.
RESULTS: IL-17 and IL-23 serum levels were higher in patients with ALS as
compared with patients with NIND (P = 0.015 and P = 0.002 respectively). IL-17
and IL-23 CSF levels were also increased in patients with ALS (P = 0.0006 and P
= 0.000001 respectively). IL-17 and IL-23 levels were not correlated with
disease duration, disability scale or clinical subtype of the disease onset in
ALS patients.
CONCLUSIONS: Our findings suggest that these molecules may be involved in the
pathogenetic mechanisms acting as potential markers of Th17 cells activation in
ALS.

Copyright © 2010 The Authors. Journal compilation © 2010 Blackwell Munksgaard.

DOI: 10.1111/j.1600-0404.2010.01333.x
PMID: 20219021 [Indexed for MEDLINE]


38. Biomed Res Int. 2013;2013:295132. doi: 10.1155/2013/295132. Epub 2013 Jul 25.

IL-17 in the rheumatologist's line of sight.

Truchetet ME(1), Mossalayi MD, Boniface K.

Author information:
(1)UMR-CNRS 5164, Composantes Innées de la Réponse Immunitaire et de la
Différenciation, Université Bordeaux Segalen, 146 rue Léo Saignat, 33076
Bordeaux, France. marie-elise.truchetet@chu-bordeaux.fr

Over the past decades, the identification of several new cytokines, including
interleukin (IL)-17 and IL-23, and of new T helper cell subsets, including Th17
cells, has changed the vision of immunological processes. The IL-17/Th17 pathway
plays a critical role during the development of inflammation and autoimmunity,
and targeting this pathway has become an attractive strategy for a number of
diseases. This review aims to describe the effects of IL-17 in the joint and its
roles in the development of autoimmune and inflammatory arthritis. Furthermore,
biotherapies targeting directly or indirectly IL-17 in inflammatory rheumatisms
will be developed.

DOI: 10.1155/2013/295132
PMCID: PMC3741932
PMID: 23984335 [Indexed for MEDLINE]


39. Seizure. 2016 May;38:17-22. doi: 10.1016/j.seizure.2016.03.006. Epub 2016 Mar
22.

The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with
intractable childhood epilepsy.

Ni FF(1), Li CR(2), Liao JX(1), Wang GB(1), Lin SF(1), Xia Y(1), Wen JL(1).

Author information:
(1)Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026,
China.
(2)Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026,
China. Electronic address: shenzhen81111@163.com.

PURPOSE: The ketogenic diet (KD) is an effective treatment for intractable
epilepsy (IE), however the therapeutic mechanism is still unclear. This study
was designed to investigate T helper type 17/regulatory T cell (Th17/Treg)
levels in children with IE and age-matched healthy controls following KD.
METHOD: Circulating levels of Th17/Treg cells were analyzed by flow cytometry.
Plasma concentration of interleukin (IL)-17 was measured by cytometric bead
array assay. Real-time PCR was performed to measure mRNA levels of mTOR, HIF1α
and Th17/Treg associated factors in purified CD4(+)CD25(+) T and CD4(+)CD25(-) T
cells.
RESULTS: By one-way ANOVA, the proportion of circulating Th17 cells and
expression of IL-17A and RORγt were significantly higher (P<.05), while the
proportion of circulating Tregs and expression of Foxp3, GITR, CTLA-4 were
significantly lower (P<.05) in IE patients than healthy subjects. However, these
alternations were reversed following KD (P<.05). In CD4(+)CD25(+) T and
CD4(+)CD25(-) T cells mTOR and HIF1α expression were significantly higher in IE
patients (P<.05), however KD reduced mTOR and HIF1α expression (P<.05). The
plasma IL-17A concentrations were higher in IE patients than controls (P<.05).
KD partially reduced IL-17A levels (P<.05).
CONCLUSION: Our results suggest that Th17/Treg imbalance is characteristic of
childhood IE, and may contribute to IE pathogenesis. KD treatment is able to
correct this imbalance, probably via inhabiting the mTOR/HIF-1α signaling
pathway.

Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All
rights reserved.

DOI: 10.1016/j.seizure.2016.03.006
PMID: 27061881 [Indexed for MEDLINE]


40. PLoS One. 2018 Jan 12;13(1):e0190850. doi: 10.1371/journal.pone.0190850.
eCollection 2018.

Utilization of peptide phage display to investigate hotspots on IL-17A and what
it means for drug discovery.

Ting JP(1), Tung F(2), Antonysamy S(2), Wasserman S(3), Jones SB(4), Zhang
FF(2), Espada A(5), Broughton H(5), Chalmers MJ(4), Woodman ME(4), Bina HA(4),
Dodge JA(4), Benach J(3), Zhang A(2), Groshong C(2), Manglicmot D(2), Russell
M(2), Afshar S(1).

Author information:
(1)Department of protein Engineering, Eli Lilly Biotechnology Center, San Diego,
California, United States of America.
(2)Department of structural Biology, Discovery Chemistry Research and
Technologies, Lilly Biotechnology Center, Eli Lilly and Company, San Diego,
California, United States of America.
(3)Department of structural Biology, Discovery Chemistry Research and
Technologies, Eli Lilly and Company, Advanced Photon Source, Argonne, Illinois,
United States of America.
(4)Lilly Research Laboratories, Indianapolis, Indiana, United States of America.
(5)Centro de Investigación Lilly, Alcobendas, Spain.

To date, IL-17A antibodies remain the only therapeutic approach to correct the
abnormal activation of the IL-17A/IL-17R signaling complex. Why is it that
despite the remarkable success of IL-17 antibodies, there is no small molecule
antagonist of IL-17A in the clinic? Here we offer a unique approach to address
this question. In order to understand the interaction of IL-17A with its
receptor, we combined peptide discovery using phage display with HDX,
crystallography, and functional assays to map and characterize hot regions that
contribute to most of the energetics of the IL-17A/IL-17R interaction. These
functional maps are proposed to serve as a guide to aid in the development of
small molecules that bind to IL-17A and block its interaction with IL-17RA.

DOI: 10.1371/journal.pone.0190850
PMCID: PMC5766103
PMID: 29329326 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: This research was funded by
Eli Lilly & Company. The funder provided support in the form of salaries for
authors [JPT, FT, SA, SW, SBJ, FFZ, AE, HB, MJC, HAB, MW, JAD, JB, AZ, CG, DM,
MR, & SA]. There are no patents, products in development or marketed products to
declare. This does not alter our adherence to all the PLOSONE policies on
sharing data and materials.


41. Int Rev Immunol. 2015;34(4):348-63. doi: 10.3109/08830185.2015.1049345.

The Evolving View of IL-17-Mediated Immunity in Defense Against Mucocutaneous
Candidiasis in Humans.

Soltész B(1), Tóth B, Sarkadi AK, Erdős M, Maródi L.

Author information:
(1)Department of Infectious Diseases and Pediatric Immunology, Faculty of
Medicine, University of Debrecen , Debrecen , Hungary.

The discovery of interleukin (IL)-17-mediated immunity has provided a robust
framework upon which our current understanding of the mechanism involved in host
defense against mucocutaneous candidiasis (CMC) has been built. Studies have
shed light on how pattern recognition receptors expressed by innate immune cells
recognize various components of Candida cell wall. Inborn errors of immunity
affecting IL-17+ T cell differentiation have recently been defined, such as
deficiencies of signal transducer and activator of transcription (STAT)3, STAT1,
IL-12Rβ1 and IL-12p40, and caspase recruitment domain 9. Impaired
receptor-ligand coupling was identified in patients with IL-17F and IL-17
receptor A (IL17RA) deficiency and autoimmune polyendocrine syndrome (APS) type
1. Mutation in the nuclear factor kappa B activator (ACT) 1 was described as a
cause of impaired IL-17R-mediated signaling. CMC may be part of a complex
clinical phenotype like in patients with deficiencies of STAT3,
IL-12Rβ1/IL-12p40 and APS-1 or may be the only or dominant phenotypic
manifestation of disease which is referred to as CMC disease. CMCD may result
from deficiencies of STAT1, IL-17F, IL-17RA and ACT1. In this review we discuss
how recent research on IL-17-mediated immunity shed light on host defense
against mucocutaneous infection by Candida and how the discovery of various
germ-line mutations and the characterization of associated clinical phenotypes
have provided insights into the role of CD4+IL-17+ lymphocytes in the regulation
of anticandidal defense of body surfaces.

DOI: 10.3109/08830185.2015.1049345
PMID: 26154078 [Indexed for MEDLINE]


42. Cell Mol Immunol. 2016 Jul;13(4):474-83. doi: 10.1038/cmi.2015.56. Epub 2015 Jul
13.

IL-17C is required for lethal inflammation during systemic fungal infection.

Huang J(1), Meng S(1), Hong S(1), Lin X(1), Jin W(1), Dong C(1).

Author information:
(1)Institute for Immunology, Tsinghua University, Beijing, 100084, China.

Within the interleukin-17 (IL-17) family of cytokines, IL-17A is known to be
critical in the host defense against fungal infections; however, the function of
the other IL-17 family members in anti-fungal immunity remains largely unknown.
Here, we show that IL-17C expression was highly induced in kidney epithelial
cells after fungal infection. Mice that lacked IL-17C exhibited increased
survival and attenuated kidney tissue damage, although they had similar fungal
loads. IL-17C deficiency resulted in decreased pro-inflammatory cytokine
expression compared with wild-type control mice. Additionally, IL-17C directly
acted on renal epithelial cells in vitro to promote pro-inflammatory cytokine
production. Taken together, our data demonstrate that IL-17C is a critical
factor that potentiates inflammatory responses and causes host injury during
fungal infection.

DOI: 10.1038/cmi.2015.56
PMCID: PMC4947823
PMID: 26166766 [Indexed for MEDLINE]


43. Arch Oral Biol. 2015 Jan;60(1):91-9. doi: 10.1016/j.archoralbio.2014.09.002.
Epub 2014 Sep 28.

Association study between salivary levels of interferon (IFN)-gamma, interleukin
(IL)-17, IL-21, and IL-22 with chronic periodontitis.

Isaza-Guzmán DM(1), Cardona-Vélez N(1), Gaviria-Correa DE(1), Martínez-Pabón
MC(1), Castaño-Granada MC(1), Tobón-Arroyave SI(2).

Author information:
(1)POPCAD Research Group, Laboratory of Immunodetection and Bioanalysis, Faculty
of Dentistry, University of Antioquia, Medellín, Colombia.
(2)POPCAD Research Group, Laboratory of Immunodetection and Bioanalysis, Faculty
of Dentistry, University of Antioquia, Medellín, Colombia. Electronic address:
stobonarroyave@hotmail.com.

OBJECTIVE: To investigate if the salivary levels of IL-17, IL-21, IL-22, and its
ratio regarding salivary IFN-γ may be linked with the periodontal clinical
status.
DESIGN: One hundred and five chronic periodontitis (CP) subjects and 44 healthy
controls (HC) were recruited. Periodontal status was assessed based on
full-mouth clinical periodontal measurements. Cytokine salivary levels were
analyzed by ELISA. The association between the analytes with CP was analyzed
using a binary logistic regression model.
RESULTS: A statistically significant increase in salivary levels of IFN-γ and
IFN-γ/IL-22 ratio in CP group could be detected, but there was no significant
domination of any Th17 cytokine that could be of predictive value for
health/disease status. Univariate and binary logistic regression analyses
revealed a strong and independent association of IFN-γ salivary levels and
IFN-γ/IL-22 ratio with disease status. An interaction effect of ageing on IFN-γ
levels also could be noted.
CONCLUSION: While salivary levels of IFN-γ and IFN-γ/IL-22 ratio may act as
strong/independent indicators of the amount and extent of periodontal breakdown,
the low detection frequency of Th17 cytokines in saliva samples make these
determinations useless for the detection of disease presence and/or its
severity.

Copyright © 2014 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.archoralbio.2014.09.002
PMID: 25285903 [Indexed for MEDLINE]


44. J Virol. 2014 Aug;88(15):8479-89. doi: 10.1128/JVI.00724-14. Epub 2014 May 14.

Interleukin-6 (IL-6) and IL-17 synergistically promote viral persistence by
inhibiting cellular apoptosis and cytotoxic T cell function.

Hou W(1), Jin YH(1), Kang HS(1), Kim BS(2).

Author information:
(1)Department of Microbiology-Immunology, Feinberg School of Medicine,
Northwestern University, Chicago, Illinois, USA.
(2)Department of Microbiology-Immunology, Feinberg School of Medicine,
Northwestern University, Chicago, Illinois, USA bskim@northwestern.edu.

Interleukin-6 (IL-6) plays an important role in the development and progression
of inflammatory responses, autoimmune diseases, and cancers. Many viral
infections, including Theiler's murine encephalomyelitis virus (TMEV), result in
the vigorous production of IL-6. However, the role of IL-6 in the development of
virus-induced inflammatory responses is unclear. The infection of susceptible
mice with TMEV induces the development of chronic demyelinating disease, which
is considered a relevant infectious model for multiple sclerosis. In this study,
we demonstrate that resistant C57BL/6 mice carrying an IL-6 transgene (IL-6 Tg)
develop a TMEV-induced demyelinating disease accompanied by an increase in viral
persistence and an elevated Th17 cell response in the central nervous system.
Either IL-6 or IL-17 induced the expression of Bcl-2 and Bcl-xL at a high
concentration. The upregulated expression of prosurvival molecules in turn
inhibited target cell destruction by virus-specific CD8(+) T cells. More
interestingly, IL-6 and IL-17 synergistically promoted the expression of these
prosurvival molecules, preventing cellular apoptosis at a much lower (<5-fold)
concentration. The signals involved in the synergy appear to include the
activation of both STAT3 and NF-κB via distinct cytokine-dependent pathways.
Thus, the excessive IL-6 promotes the generation of Th17 cells, and the
resulting IL-6 and IL-17 synergistically promote viral persistence by protecting
virus-infected cells from apoptosis and CD8(+) T cell-mediated target
destruction. These results suggest that blocking both IL-6 and IL-17 functions
are important considerations for therapies of chronic viral diseases, autoimmune
diseases, and cancers.
IMPORTANCE: This study indicates that an excessive level of IL-6 cytokine
produced following viral infection promotes the development of IL-17-producing
pathogenic helper T cells. We demonstrate here for the first time that IL-6
together with IL-17 synergistically enhances the expression of survival
molecules to hinder critical host defense mechanisms removing virus-infected
cells. This finding has an important implication in controlling not only chronic
viral infections but also autoimmune diseases and cancers, which are associated
with prolonged cell survival.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

DOI: 10.1128/JVI.00724-14
PMCID: PMC4135960
PMID: 24829345 [Indexed for MEDLINE]


45. Sci Rep. 2018 Nov 26;8(1):17374. doi: 10.1038/s41598-018-35783-9.

Ternary crystal structure of human RORγ ligand-binding-domain, an inhibitor and
corepressor peptide provides a new insight into corepressor interaction.

Noguchi M(1), Nomura A(2), Doi S(2), Yamaguchi K(2), Hirata K(3), Shiozaki M(3),
Maeda K(3), Hirashima S(3), Kotoku M(3), Yamaguchi T(4), Katsuda Y(4), Crowe
P(5), Tao H(5), Thacher S(5), Adachi T(6).

Author information:
(1)Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical
Research Institute, Japan Tobacco Inc., 1-13-2, Fukuura, Kanazawa-Ku, Yokohama,
Kanagawa, 236-0004, Japan. masato.noguchi@jt.com.
(2)Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical
Research Institute, Japan Tobacco Inc., 1-13-2, Fukuura, Kanazawa-Ku, Yokohama,
Kanagawa, 236-0004, Japan.
(3)Chemical Research Laboratories, Central Pharmaceutical Research Institute,
Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka, 569-1125, Japan.
(4)Biological Pharmacological Research Laboratories, Central Pharmaceutical
Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka,
569-1125, Japan.
(5)Orphagen Pharmaceuticals, 11558 Sorrento Valley Road, Suite 4, San Diego,
California, 92121, USA.
(6)Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical
Research Institute, Japan Tobacco Inc., 1-13-2, Fukuura, Kanazawa-Ku, Yokohama,
Kanagawa, 236-0004, Japan. tsuyoshi.adachi@jt.com.

Retinoic acid-related orphan receptor gamma (RORγ) plays pivotal roles in
autoimmune diseases by controlling the lineage of interleukin 17
(IL-17)-producing CD4+ T cells (Th17 cells). Structure-based drug design has
proven fruitful in the development of inhibitors targeting the ligand binding
domain (LBD) of RORγ. Here, we present the crystal structure of a novel RORγ
inhibitor co-complex, in the presence of a corepressor (CoR) peptide. This
ternary complex with compound T reveals the structural basis for an inhibitory
mechanism different from the previously reported inverse agonist. Compared to
the inverse agonist, compound T induces about 2 Å shift of helix 5 (H5) backbone
and side-chain conformational changes of Met365 on H5. These conformational
changes correlate to reduced CoR peptide binding to RORγ-LBD in the presence of
compound T, which suggests that the shift of H5 is responsible. This crystal
structure analysis will provide useful information for the development of novel
and efficacious drugs for autoimmune disorders.

DOI: 10.1038/s41598-018-35783-9
PMCID: PMC6255837
PMID: 30478402 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.


46. Mediators Inflamm. 2016;2016:2839232. doi: 10.1155/2016/2839232. Epub 2016 Aug
17.

Interferon Tau Affects Mouse Intestinal Microbiota and Expression of IL-17.

Ren W(1), Chen S(2), Zhang L(3), Liu G(2), Hussain T(2), Hao X(2), Yin J(2),
Duan J(2), Tan B(2), Wu G(4), Bazer FW(4), Yin Y(2).

Author information:
(1)Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute
of Subtropical Agriculture, Chinese Academy of Sciences, Observation and
Experiment Station of Animal Nutrition and Feed Science in South-Central China,
Ministry of Agriculture, Hunan Provincial Engineering Research Center for
Healthy Livestock and Poultry Production, Changsha, Hunan 410125, China;
University of the Chinese Academy of Sciences, Beijing 10008, China.
(2)Key Laboratory of Agro-Ecological Processes in Subtropical Region, Institute
of Subtropical Agriculture, Chinese Academy of Sciences, Observation and
Experiment Station of Animal Nutrition and Feed Science in South-Central China,
Ministry of Agriculture, Hunan Provincial Engineering Research Center for
Healthy Livestock and Poultry Production, Changsha, Hunan 410125, China.
(3)Jinan First People's Hospital, Shandong 250011, China.
(4)Department of Animal Science, Texas A&M University, 2471 TAMU, College
Station, TX 77843-2471, USA.

This study was conducted to explore the effects of interferon tau (IFNT) on the
intestinal microbiota and expression of interleukin 17 (IL-17) in the intestine
of mice. IFNT supplementation increased microbial diversity in the jejunum and
ileum but decreased microbial diversity in the feces. IFNT supplementation
influenced the composition of the intestinal microbiota as follows: (1)
decreasing the percentage of Firmicutes and increasing Bacteroidetes in the
jejunum and ileum; (2) enhancing the percentage of Firmicutes but decreasing
Bacteroidetes in the colon and feces; (3) decreasing Lactobacillus in the
jejunum and ileum; (4) increasing the percentage of Blautia, Bacteroides,
Alloprevotella, and Lactobacillus in the colon; and (5) increasing the
percentage of Lactobacillus, Bacteroides, and Allobaculum, while decreasing
Blautia in the feces. Also, IFNT supplementation decreased the expression of
IL-17 in the intestines of normal mice and of an intestinal pathogen infected
mice. In conclusion, IFNT supplementation modulates the intestinal microbiota
and intestinal IL-17 expression, indicating the applicability of IFNT to treat
the intestinal diseases involving IL-17 expression and microbiota.

DOI: 10.1155/2016/2839232
PMCID: PMC5005528
PMID: 27610003 [Indexed for MEDLINE]


47. Cell Signal. 2007 Jul;19(7):1514-20. doi: 10.1016/j.cellsig.2007.01.025. Epub
2007 Feb 6.

Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via
TRAF6.

Rong Z(1), Cheng L, Ren Y, Li Z, Li Y, Li X, Li H, Fu XY, Chang Z.

Author information:
(1)Department of Biological Sciences and Biotechnology, School of Medicine,
Institute of Biomedicine, State Key Laboratory of Biomembrane and Membrane
Biotechnology, Tsinghua University, Beijing 100084, China.

Interleukin-17F (IL-17F), together with interleukin-17A (IL-17 or IL-17A), is a
marker of T(H)17 cells, a new lineage of effector CD4(+) T cells to contribute
to pathogenesis of a growing list of autoimmune and inflammatory diseases, such
as experimental autoimmune encephalitis (EAE) and collagen-induced arthritis
(CIA). IL-17F, similar to IL-17A, was reported to employ interleukin-17 receptor
(IL-17R or IL-17RA) for signaling but the downstream cascades remain largely
elusive. Here we report that TRAF6 interacts with IL-17R and mediates
ubiquitination of the receptor. We observed that IL-17F and IL-17A could induce
IL-17R ubiquitination and DN-TRAF6, a dominant-negative mutant, could block
IL-17F- but not IL-17A-triggered ubiquitination of IL-17R. Moreover, we showed
that the ubiquitination of IL-17R was positively correlated with the downstream
signaling, as evaluated by a luciferase reporter driven by a putative native
promoter of 24p3, an IL-17 targeted gene. Our results indicate that
ubiquitination of IL-17R mediated by TRAF6 plays a critical role in IL-17F
signaling. This study, for the first time, reveals a possible molecular
mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires
the receptor ubiquitination by TRAF6.

DOI: 10.1016/j.cellsig.2007.01.025
PMID: 17346928 [Indexed for MEDLINE]


48. J Heart Lung Transplant. 2003 Nov;22(11):1280-3. doi:
10.1016/s1053-2498(02)01234-2.

Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle
cells in vitro: a potential role for interleukin-17 and airway smooth muscle
cells in bronchiolitis obliterans syndrome.

Vanaudenaerde BM(1), Wuyts WA, Dupont LJ, Van Raemdonck DE, Demedts MM, Verleden
GM.

Author information:
(1)Laboratory of Pneumology, Catholic University Leuven, Leuven, Belgium.

Bronchiolitis obliterans syndrome is the major constraint on the long-term
survival after lung transplantation. Both neutrophils and interleukin (IL)-8, a
potent neutrophil attractant, have been shown to play an important role in the
pathophysiology of obliterative bronchiolitis. We investigated the potential
role of human airway smooth muscle cells in obliterative bronchiolitis by
studying their release of IL-8 after stimulation with IL-17, a novel
T-cell-derived chemokine capable of attracting and activating neutrophils. We
demonstrated a significant increase in IL-8 release, reaching a concentration of
86.6 ng/ml (SEM 1.9 ng/ml) with 100 ng/ml IL-17 (p < 0.01, n = 4), as compared
with non-stimulated cells. This IL-17-mediated IL-8 release could not be
inhibited by dexamethasone. We conclude that human airway smooth muscle cells
may play an important pro-inflammatory role in neutrophilic inflammatory
diseases such as chronic rejection after lung transplantation; furthermore,
IL-17 may be the link between lymphocytes and neutrophils.

DOI: 10.1016/s1053-2498(02)01234-2
PMID: 14585390 [Indexed for MEDLINE]


49. Curr Protoc Immunol. 2007 Nov;Chapter 6:Unit 6.25. doi:
10.1002/0471142735.im0625s79.

Measurement of interleukin-17.

Pappu BP(1), Dong C.

Author information:
(1)M.D. Anderson Cancer Center, Houston, Texas, USA.

Upon antigenic stimulation, naive CD4+ T cells undergo proliferation and
differentiate into cytokine-producing T helper (T(H)) effector cells. T(H)1
cells secrete effector cytokine IFN-gamma and regulate cell-mediated immunity,
whereas T(H)2 cells produce IL-4, IL-5, and IL-13 cytokines, and mediate
immunity against extracellular pathogens and allergic reactions. Recent studies
have identified a novel T(H) subset, called T(H)17, TH(IL-17), or inflammatory
T(H) (THi) cells, characterized by the production of a proinflammatory cytokine,
IL-17, and regulating inflammatory responses. In this unit, we describe the
protocols for the differentiation of mouse IL-17-expressing T cells in vitro,
detection of IL-17-expressing T cells by intracellular cytokine staining, and
measurement of IL-17 secretion in culture supernatants by ELISA. Generation of
IL-17-expressing T cells in vitro under defined culture conditions allows
investigation of their differentiation regulation. Detection of IL-17 in cell
culture and tissue samples helps in monitoring inflammatory diseases and
determining efficacy of therapeutic interventions.

(c) 2007 by John Wiley & Sons, Inc.

DOI: 10.1002/0471142735.im0625s79
PMID: 18432994 [Indexed for MEDLINE]


50. Int J Immunopathol Pharmacol. 2004 Jan-Apr;17(1):1-4. doi:
10.1177/039463200401700101.

Interleukin-17: a revisited study.

Huang SH, Frydas S, Conti P, Kempuraj D, Barbacane RC, Grilli A, Boucher W,
Letourneau R, Papadopoulou N, Donelan J, Madhappan B, Theoharides TC, De Lutiis
MA, Riccioni G, Sabatino G.

DOI: 10.1177/039463200401700101
PMID: 15000860 [Indexed for MEDLINE]


51. J Med Microbiol. 2016 Aug;65(8):821-827. doi: 10.1099/jmm.0.000273. Epub 2016
May 10.

Endogenous IL-17 as a factor determining the severity of Clostridium difficile
infection in mice.

Nakagawa T(1)(2), Mori N(1), Kajiwara C(1), Kimura S(1), Akasaka Y(3), Ishii
Y(1), Saji T(2), Tateda K(1).

Author information:
(1)Department of Microbiology and Infectious Diseases, Toho University School of
Medicine, Tokyo, Japan.
(2)Division of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan.
(3)Division of Chronic Inflammatory Diseases, Advanced Medical Research Center,
Toho University Graduate School of Medicine, Tokyo, Japan.

Clostridium difficile infection (CDI) is a toxin-mediated intestinal disease.
Toxin A, toxin B and binary toxin are believed to be responsible for the
pathogenesis of CDI, which is characterized by massive infiltration of
neutrophils at the infected intestinal mucosa. IL-17 is one of the cytokines
that play critical roles in several inflammatory and immunological diseases
through various actions, including promoting neutrophil recruitment. The aim of
this study was to examine the role of this cytokine in CDI by employing IL-17 A
and F double knockout (IL-17 KO) mice for the CDI model. We demonstrated that
IL-17 KO mice were more resistant to CDI than WT mice using several factors,
such as diarrhoea score, weight change and survival rate. Although the bacterial
numbers of C. difficile in faeces were not different, the inflammatory mediator
levels at the large intestine on day 3 post-infection were attenuated in IL-17
KO mice. Finally, we showed that infiltration of neutrophils, but not
macrophages, in the large intestine was significantly decreased in IL-17 KO mice
compared to WT mice. In conclusion, the data demonstrate that endogenous IL-17
may be a factor determining the severity of CDI in mice. Although the mechanism
is totally unknown, IL-17-mediated inflammatory responses, such as
cytokine/chemokine production and neutrophil accumulation, may be plausible
targets for future investigations.

DOI: 10.1099/jmm.0.000273
PMID: 27166143 [Indexed for MEDLINE]


52. J Int Med Res. 2009 May-Jun;37(3):862-6. doi: 10.1177/147323000903700331.

Myeloperoxidase (MPO) and interleukin-17 (IL-17) plasma levels are increased in
patients with acute coronary syndromes.

Liang J(1), Zheng Z, Wang M, Han L, Zheng Z, Peng J, Liu Z, Wei Y.

Author information:
(1)Cardiology Department, The First Affiliated Hospital of Nanchang University,
Nanchang, Jiangxi, China.

There are several reports of myeloperoxidase (MPO) playing an important role in
acute coronary syndromes (ACS). Interleukin-17 (IL-17) is a pro-inflammatory
cytokine produced by activated CD4 T cells that has a chemotactic and activating
effect on neutrophils. It has also been shown that IL-17 recruits neutrophils
via the release of C-X-C chemokines. The roles of MPO and IL-17 in ACS, however,
have not been established. This study measured plasma MPO and IL-17 levels in 10
patients with ACS, 11 age- and sex-matched patients with stable angina and 12
healthy control subjects. Plasma MPO and IL-17 levels were significantly
elevated in ACS patients compared with the patients with stable angina and the
healthy control subjects. In addition, plasma MPO levels correlated with plasma
IL-17 levels in all study participants. It is concluded that MPO and IL-17 are
powerful indicators of acute coronary inflammation, however the data set was
very small, so larger prospective studies are required.

DOI: 10.1177/147323000903700331
PMID: 19589271 [Indexed for MEDLINE]


53. Transplant Proc. 2009 Jun;41(5):1562-4. doi: 10.1016/j.transproceed.2009.01.092.

Interleukin-17 and kidney allograft outcome.

Crispim JC(1), Grespan R, Martelli-Palomino G, Rassi DM, Costa RS, Saber LT,
Cunha FQ, Donadi EA.

Author information:
(1)Department of Biochemistry and Immunology, School of Medicine of Ribeirão
Preto, University of São Paulo, (FMRP-USP), São Paulo, Brazil.
janacrispim@usp.br

Acute rejection episodes (ARE) are important complications that involve the
interplay between mechanisms that maintain graft tolerance and promote
rejection. The proinflammatory cytokine interleukin-17 (IL-17) has been
implicated in many conditions in humans and mice. In kidney transplant patients,
the evaluation IL-17 levels has been performed in only a few patients. We
performed a cross-sectional study correlating quantitative IL-17 levels and
clinical outcomes.
PATIENTS AND METHODS: We studied 19 specimens from biopsies performed in
patients (n = 19) who received isolated kidney grafts. ARE signs were present in
9 (47%) patients who provide specimens; whereas, 10 (53%) others showed no signs
of rejection. Eighteen healthy control sample IL-17 underwent measurement, all
of which were performed by an enzyme-linked immunosorbent assay method. We
assessed other factors, such as the recipients demographic data, cold ischemia
time, HLA mismatches, time elapsed from transplantation to the biopsy,
posttransplantation status, antibody panel, donor type, and immunosuppressive
treatment.
RESULTS: IL-17 levels were clearly increased among samples derived from patients
with ongoing rejection (125.7 +/- 27.06 pg/mL) in contrast, to the nonrejection
group, (30 +/- 13.32 pg/mL) (P < .05). Healthy controls showed no detectable
IL-17 levels.
CONCLUSIONS: These findings suggested that IL-17 was important in the
pathophysiology of acute kidney rejection.

DOI: 10.1016/j.transproceed.2009.01.092
PMID: 19545679 [Indexed for MEDLINE]


54. J Immunol. 2019 Mar 1;202(5):1540-1548. doi: 10.4049/jimmunol.1801025. Epub 2019
Jan 25.

IL-17A Recruits Rab35 to IL-17R to Mediate PKCα-Dependent Stress Fiber Formation
and Airway Smooth Muscle Contractility.

Bulek K(1)(2), Chen X(3), Parron V(4), Sundaram A(5), Herjan T(3)(6), Ouyang
S(3), Liu C(3), Majors A(3), Zepp J(3), Gao J(7), Dongre A(7), Bodaszewska-Lubas
M(2), Echard A(8), Aronica M(3), Carman J(7), Garantziotis S(4), Sheppard D(5),
Li X(1).

Author information:
(1)Department of Inflammation and Immunity, Lerner Research Institute, Cleveland
Clinic Foundation, Cleveland, OH 44195; bulekk@ccf.org lix@ccf.org.
(2)Department of Immunology, Faculty of Biochemistry, Biophysics, and
Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.
(3)Department of Inflammation and Immunity, Lerner Research Institute, Cleveland
Clinic Foundation, Cleveland, OH 44195.
(4)Division of Intramural Research, National Institute of Environmental Health
Sciences, Research Triangle Park, NC 27709.
(5)Lung Biology Center, University of California San Francisco, San Francisco,
CA 94143.
(6)Department of General Biochemistry, Faculty of Biochemistry, Biophysics and
Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.
(7)Discovery Biology, Bristol-Myers Squibb, Princeton, NJ 08543; and.
(8)Membrane Traffic and Cell Division Lab, Cell Biology and Infection
Department, Pasteur Institute, 75015 Paris, France.

IL-17A is a critical proinflammatory cytokine for the pathogenesis of asthma
including neutrophilic pulmonary inflammation and airway hyperresponsiveness. In
this study, by cell type-specific deletion of IL-17R and adaptor Act1, we
demonstrated that IL-17R/Act1 exerts a direct impact on the contraction of
airway smooth muscle cells (ASMCs). Mechanistically, IL-17A induced the
recruitment of Rab35 (a small monomeric GTPase) and DennD1C (guanine nucleotide
exchange factor [GEF]) to the IL-17R/Act1 complex in ASMCs, resulting in
activation of Rab35. Rab35 knockdown showed that IL-17A-induced Rab35 activation
was essential for protein kinase Cα (PKCα) activation and phosphorylation of
fascin at Ser39 in ASMCs, allowing F-actin to interact with myosin to form
stress fibers and enhance the contraction induced by methacholine. PKCα
inhibitor or Rab35 knockdown indeed substantially reduced IL-17A-induced stress
fiber formation in ASMCs and attenuated IL-17A-enhanced, methacholine-induced
contraction of airway smooth muscle. Taken together, these data indicate that
IL-17A promotes airway smooth muscle contraction via direct recruitment of Rab35
to IL-17R, followed by PKCα activation and stress fiber formation.

Copyright © 2019 by The American Association of Immunologists, Inc.

DOI: 10.4049/jimmunol.1801025
PMCID: PMC6379809
PMID: 30683702 [Indexed for MEDLINE]


55. Cytokine. 2011 Dec;56(3):717-25. doi: 10.1016/j.cyto.2011.09.010. Epub 2011 Oct
12.

Increased interleukin (IL)-8 and decreased IL-17 production in chronic
obstructive pulmonary disease (COPD) provoked by cigarette smoke.

Zhang X(1), Zheng H, Zhang H, Ma W, Wang F, Liu C, He S.

Author information:
(1)The General Hospital of PLA, Beijing 100853, China.

Recently, involvement of IL-17 in development of COPD has been noticed. Unlike
IL-8, the role of IL-17 in COPD remains controversial. In order to further
understand mechanisms in cigarette smoke (CS) induced COPD, we investigated
IL-17 and IL-8 levels in different stages of COPD patients, and time courses of
IL-17 and IL-8 release in CS induced COPD rats. A total of 73 elderly patients
with COPD and 31 healthy volunteers were recruited in the study. IL-17 and IL-8
levels in the sputum and plasma were measured, and number of differential cells
was counted. A newly developed CS induced rat COPD model was employed to study
time courses of IL-17 and IL-8 release and nucleated cell accumulation. The
results showed that IL-8 levels in the sputum of severe COPD patients were
elevated by 16.5-fold, but IL-17 levels were reduced by 4.8-fold. While IL-8
correlated with neutrophils, IL-17 correlated with monocytes and lymphocytes.
Similarly, level of IL-8 was increased, but IL-17 was decreased in the
bronchoalveolar lavage fluid (BALF) of CS rats. Time course study showed that
increased IL-8 production in the BALF initiated at 6 weeks, but decreased IL-17
production started at 10 weeks following CS exposure. In conclusion, increased
IL-8 level in COPD patients appears mainly secreted from neutrophils and
macrophages, whereas decreased IL-17 level seems resulted from reduced number of
monocytes or damaged epithelial cells. Increased IL-8 (a proinflammatory
cytokine) secretion and decreased IL-17 (a protective cytokine of airways)
release can both contribute to development of COPD.

Copyright © 2011 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.cyto.2011.09.010
PMID: 21996014 [Indexed for MEDLINE]


56. Clin Exp Rheumatol. 2005 Jul-Aug;23(4 Suppl 38):S77-80.

Serum interleukin 17 and interleukin 18 levels in familial Mediterranean fever.

Haznedaroglu S(1), Oztürk MA, Sancak B, Goker B, Onat AM, Bukan N, Ertenli I,
Kiraz S, Calguneri M.

Author information:
(1)Department of Rheumatology, Gazi University School of Medicine, Ankara,
Turkey.

OBJECTIVE: Familial Mediterranean fever (FMF) attacks are characterized by
serosal inflammation rich in PMNL leukocytes and activation of a definite
cytokine network. Moreover, there is sustained inflammation in attack-free FMF
patients. Interleukin (IL)-17 and IL-18 are recently described proinflammatory
cytokines, which can modulate certain neutrophil functions. In this study we
measured serum levels of IL-17 and IL-18 in FMF patients.
METHODS: The study groups comprised of 18 FMF patients in attack-free period
(mean age: 30.2 +/- 9.5 years; male/female: 10/8), and 18 patients with an acute
FMF attack (mean age: 25.4 +/- 4.9 years; male/female: 10/8). Twenty age-matched
healthy subjects were included as a control group (male/female: 10/10). Levels
of IL-17 and IL-18 were determined by commercial ELISA kits (Biosource
International, USA).
RESULTS: Serum IL-17 levels were 42.8 +/- 3.7, 42.7 +/- 3.2, and 39.9 +/- 2.3
pg/mL for FMF patients in attack-free period, FMF patients with acute attack,
and healthy controls, respectively. Serum IL-18 levels were 878.8 +/- 315.0,
854.2 +/- 261.4, and 314.6 +/- 80.8 pg/mL for FMF patients in an attack-free
period, FMF patients with acute attack, and healthy controls, respectively.
Levels of both IL-17 and IL-18 were significantly higher in FMF patients with
and without acute attack compared to control group (p < 0.05). Concentrations of
those cytokines were comparable in FMF patients with acute attack and in
attack-free period (p > 0.05).
CONCLUSION: Our data suggest that IL-17 and IL-18 contribute to the cytokine
network in the inflammatory cascade of FMF. However, their roles for the
initiation of FMF attacks remain to be established.

PMID: 16273770 [Indexed for MEDLINE]


57. J Neuroinflammation. 2017 Jan 23;14(1):20. doi: 10.1186/s12974-016-0784-3.

Th17-skewed immune response and cluster of differentiation 40 ligand expression
in canine steroid-responsive meningitis-arteritis, a large animal model for
neutrophilic meningitis.

Freundt-Revilla J(1)(2), Maiolini A(3), Carlson R(3), Beyerbach M(4),
Rentmeister K(5), Flegel T(6), Fischer A(7), Tipold A(3)(8).

Author information:
(1)Department of Small Animal Medicine and Surgery, University of Veterinary
Medicine, Bünteweg 9, 30559, Hannover, Germany.
jessica.freundt.revilla@tiho-hannover.de.
(2)Center for Systems Neuroscience, Hannover, Germany.
jessica.freundt.revilla@tiho-hannover.de.
(3)Department of Small Animal Medicine and Surgery, University of Veterinary
Medicine, Bünteweg 9, 30559, Hannover, Germany.
(4)Institute for Biometry, Epidemiology and Information Processing, University
of Veterinary Medicine, Hannover, Germany.
(5)Tierärztliche Praxis für Neurologie, Dettelbach, Germany.
(6)Department of Small Animal Medicine, University of Leipzig, Leipzig, Germany.
(7)Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU
Munich, Munich, Germany.
(8)Center for Systems Neuroscience, Hannover, Germany.

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is an immune-mediated
disorder characterized by neutrophilic pleocytosis and an arteritis particularly
in the cervical leptomeninges. Previous studies of the disease have shown
increased levels of IL-6 and TGF-ß1 in cerebrospinal fluid (CSF). In the
presence of these cytokines, naive CD4+ cells differentiate into Th17
lymphocytes which synthesize interleukin 17 (IL-17). It has been shown that
IL-17 plays an active role in autoimmune diseases, it induces and mediates
inflammatory responses and has an important role in recruitment of neutrophils.
The hypothesis of a Th17-skewed immune response in SRMA should be supported by
evaluating IL-17 and CD40L, inducing the vasculitis.
METHODS: An enzyme-linked immunosorbent assay (ELISA) was performed to measure
IL-17 and CD40L in serum and CSF from a total of 79 dogs. Measurements of
patients suffering from SRMA in the acute state (SRMA A) were compared with
levels of patients under treatment with steroids (SRMA T), recurrence of the
disease (SRMA R), other neurological disorders, and healthy dogs, using the
two-part test. Additionally, secretion of IL-17 and interferon gamma (IFN-γ)
from the peripheral blood mononuclear cells (PBMCs) was confirmed by an
enzyme-linked immunospot (ELISpot) assay.
RESULTS: Significant higher levels of IL-17 were found in CSF of dogs with SRMA
A compared with SRMA T, other neurological disorders and healthy dogs
(p < 0.0001). In addition, levels of CD40L in CSF in dogs with SRMA A and SRMA R
were significantly higher than in those with SRMA T (p = 0.0004) and healthy
controls (p = 0.014). Furthermore, CSF concentrations of IL-17 and CD40L showed
a strong positive correlation among each other (rSpear = 0.6601; p < 0.0001) and
with the degree of pleocytosis (rSpear = 0.8842; p < 0.0001 and rSpear = 0.6649;
p < 0.0001, respectively). IL-17 synthesis from PBMCs in SRMA patients was
confirmed; however, IL-17 is mainly intrathecally produced.
CONCLUSIONS: These results imply that Th17 cells are inducing the autoimmune
response in SRMA and are involved in the severe neutrophilic pleocytosis and
disruption of the blood-brain barrier (BBB). CD-40L intrathecal synthesis might
be involved in the striking vasculitis. The investigation of the role of IL-17
in SRMA might elucidate important pathomechanism and open new therapeutic
strategies.

DOI: 10.1186/s12974-016-0784-3
PMCID: PMC5260073
PMID: 28114998 [Indexed for MEDLINE]


58. Braz J Psychiatry. 2017 Oct 19;40(2):212-215. doi: 10.1590/1516-4446-2017-2299.
Print 2018 Apr-June.

Plasma IL-17A levels in patients with late-life depression.

Saraykar S(1), Cao B(1), Barroso LS(2), Pereira KS(3), Bertola L(2), Nicolau
M(2), Ferreira JD(2), Dias NS(2), Vieira EL(4), Teixeira AL(1)(4), Silva APM(2),
Diniz BS(1)(2).

Author information:
(1)Department of Psychiatry and Behavioral Sciences, McGovern Medical School at
the University of Texas Health Science Center at Houston, Houston, TX, USA.
(2)Programa de Pós-Graduação em Medicina Molecular, Universidade Federal de
Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
(3)Psychiatry Department, Instituto de Previdência dos Servidores do Estado de
Minas Gerais (IPSEMG), Belo Horizonte, MG, Brazil.
(4)Divisão de Neurociências, Laboratório Interdisciplinar de Investigação
Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil.

OBJECTIVE: A consistent body of research has confirmed that patients with major
depressive disorder (MDD) have increased concentrations of pro-inflammatory
cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and
C-reactive protein, compared to controls; however, there is limited information
on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e.,
patients with late-life depression (LLD), is conspicuously missing from the
literature. The purpose of this study was to investigate the role of IL-17A in
LLD.
METHODS: A convenience sample of 129 individuals, 74 with LLD and 55
non-depressed controls, were enrolled in this study. The Mann-Whitney U test was
used to compare plasma IL-17A levels between LLD and controls subjects, and
Spearman's rank order correlation was used to investigate correlation of these
levels with clinical, neuropsychological, and cognitive assessments.
RESULTS: Plasma IL-17A levels were not statistically different between LLD
patients and controls (p = 0.94). Among all subjects (LLD + control), plasma
IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p
= 0.92) but a significant correlation was observed with cognitive assessments
(rho = 0.22, p = 0.01).
CONCLUSION: Our findings do not support an association between plasma IL-17A
levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment
in LLD patients. If this finding is confirmed in future longitudinal studies,
modulation of the T-helper 17 cell (Th17) immune response may be a treatment
target for cognitive impairment in this population.

DOI: 10.1590/1516-4446-2017-2299
PMCID: PMC6900762
PMID: 29069253 [Indexed for MEDLINE]

Conflict of interest statement: The authors report no conflicts of interest.


59. Placenta. 2007 Jan;28(1):59-63. doi: 10.1016/j.placenta.2006.01.016. Epub 2006
Mar 20.

Interleukin-17 expression in the human placenta.

Pongcharoen S(1), Somran J, Sritippayawan S, Niumsup P, Chanchan P, Butkhamchot
P, Tatiwat P, Kunngurn S, Searle RF.

Author information:
(1)Department of Medicine, Naresuan University, Phitsanulok, Thailand.

Interleukin (IL)-17 is a proinflammatory cytokine with pleiotropic activities
including inducing neovascularization and production of proangiogenic molecules.
As pregnancy outcome depends on the balance of Th1-like/Th2-like cytokines and
an increased blood supply to the fetoplacental unit, the expression of IL-17
mRNA and protein in human placental tissues was investigated. IL-17 mRNA was
expressed by purified cytokeratin-positive term placental trophoblast cells,
HLA-G+ extravillous trophoblast cells and placental macrophages (Hofbauer
cells). IL-17 localized in both cyto- and syncytiotrophoblasts of normal term
pregnancy, spontaneous miscarriage and in molar pregnancy. In spontaneous
miscarriage and molar pregnancy extravillous trophoblast cells were consistently
immunoreactive for IL-17. IL-17 expression in human placenta may play a key role
in angiogenesis and/or immunoregulation in the establishment of pregnancy.

DOI: 10.1016/j.placenta.2006.01.016
PMID: 16549200 [Indexed for MEDLINE]


60. PLoS One. 2013;8(3):e58161. doi: 10.1371/journal.pone.0058161. Epub 2013 Mar 5.

Interleukin-17 expression positively correlates with disease severity of lupus
nephritis by increasing anti-double-stranded DNA antibody production in a lupus
model induced by activated lymphocyte derived DNA.

Wen Z(1), Xu L, Xu W, Yin Z, Gao X, Xiong S.

Author information:
(1)Institute for Immunobiology, Shanghai Medical College of Fudan University,
Shanghai, China.

Lupus nephritis is one of the most serious manifestations and one of the
strongest predictors of a poor outcome in systemic lupus erythematosus (SLE).
Recent evidence implicated a potential role of interlukin-17 (IL-17) in the
pathogenesis of lupus nephritis. However, the correlation between IL-17
expression level and the severity of lupus nephritis still remains incompletely
understood. In this study, we found that serum IL-17 expression level was
associated with the severity of lupus nephritis, which was evaluated by
histopathology of kidney sections and urine protein. Of note, we showed that
enforced expression of IL-17 using adenovirus construct that expresses IL-17
could enhance the severity of lupus nephritis, while blockade of IL-17 using
neutralizing antibody resulted in decreased severity of lupus nephritis.
Consistently, we observed an impaired induction of lupus nephritis in
IL-17-deficient mice. Further, we revealed that IL-17 expression level was
associated with immune complex deposition and complement activation in kidney.
Of interest, we found that IL-17 was crucial for increasing anti-double-stranded
DNA (dsDNA) antibody production in SLE. Our results suggested that IL-17
expression level positively correlated with the severity of lupus nephritis, at
least in part, because of its contribution to anti-dsDNA antibody production.
These findings provided a novel mechanism for how IL-17 expression level
correlated with disease pathogenesis and suggested that management of IL-17
expression level was a potential and promising approach for treatment of lupus
nephritis.

DOI: 10.1371/journal.pone.0058161
PMCID: PMC3589375
PMID: 23472149 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have declared
that no competing interests exist.


61. J Reprod Immunol. 2017 Sep;123:1-2. doi: 10.1016/j.jri.2017.08.007. Epub 2017
Aug 24.

Effect of diabetes mellitus on the quality and cytokine content of human semen.

Lu X(1), Huang Y(1), Zhang H(1), Zhao J(2).

Author information:
(1)Reproductive Center, The 2nd Affiliated Hospital of Wenzhou Medical
University, 109 College Road West, Wenzhou, 325027, China.
(2)Reproductive Center, The 2nd Affiliated Hospital of Wenzhou Medical
University, 109 College Road West, Wenzhou, 325027, China. Electronic address:
zhaojzwz@126.com.

The effects of diabetes mellitus (DM) on the quality and cytokine levels of
human semen remain unknown. Sixty semen samples from 30 normal volunteers and 30
DM patients were assayed. The percentage of sperm progressive motility, sperm
vitality, sperm survival rate, the rate of normal sperm morphology, semen
volume, and semen pH and density of DM males were significantly lower than those
of normal males (p<0.05). Moreover, semen interleukin (IL)-17 and IL-18 levels
in DM males were significantly higher than those in normal males (p<0.05) and
were positively correlated with blood glucose level and sperm DNA fragmentation
index. DM increased blood glucose levels, consequently inducing the abnormal
expression of IL-17 and IL-18. The abnormal expression of these cytokines in
semen decreased semen quality and might lead to male infertility.

Copyright © 2017 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jri.2017.08.007
PMID: 28858634 [Indexed for MEDLINE]


62. Int J Mol Sci. 2019 Oct 12;20(20):5072. doi: 10.3390/ijms20205072.

Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in
Ventilator-Associated Pneumonia.

De Winter FHR(1), 's Jongers B(1), Bielen K(1)(2), Mancuso D(1)(2), Timbermont
L(2), Lammens C(2), Van Averbeke V(1), Boddaert J(1), Ali O(3), Kluytmans J(4),
Ruzin A(3), Malhotra-Kumar S(2), Jorens PG(5), Goossens H(2), Kumar-Singh
S(6)(7).

Author information:
(1)Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty
of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1,
B-2610 Wilrijk, Belgium
(2)Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute,
University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium
(3)Microbial Sciences, R&D BioPharmaceuticals, AstraZeneca, Gaithersburg, MD
20877, USA
(4)Julius Center for Health Sciences and Primary Care, University Medical Center
Utrecht, HP Stratenum 6.131, PO Box 85500, 3508 GA Utrecht, The Netherlands
(5)Department of Critical Care Medicine, Antwerp University Hospital and
University of Antwerp, LEMP, Wilrijkstraat 10, B-2650 Edegem, Belgium
(6)Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty
of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1,
B-2610 Wilrijk, Belgium. samir.kumarsingh@uantwerpen.be
(7)Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute,
University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
samir.kumarsingh@uantwerpen.be

Mechanical ventilation (MV) is the primary risk factor for the development of
ventilator-associated pneumonia (VAP). Besides inducing a pro-inflammatory
T-helper (Th)-1 cytokine response, MV also induces an anti-inflammatory Th2
cytokine response, marked by increased IL-4 secretion and reduced bacterial
phagocytic capacity of rodent lung macrophages. Since IL-4 is known to
downregulate both Th1 and Th17 cytokines, the latter is important in mediating
mucosal immunity and combating bacterial and fungal growth, we studied and
showed here in a rat model of MV that Th17 cytokines (IL-17A, IL-17F, and IL-22)
were significantly upregulated in the lung as a response to different MV
strategies currently utilized in clinic. To study whether the increased IL-4
levels are associated with downregulation of the anti-bacterial Th17 cytokines,
we subsequently challenged mechanically ventilated rats with an intratracheal
inoculation of Pseudomonas aeruginosa (VAP model) and showed a dramatic
downregulation of IL-17A, IL-17F, and IL-22, compared to animals receiving the
same bacterial burden without MV. For the studied Th1 cytokines (IFN, TNF, IL-6,
and IL-1), only IFN showed a significant decrease as a consequence of bacterial
infection in mechanically ventilated rats. We further studied IL-17A, the most
studied IL-17 family member, in intensive care unit (ICU) pneumonia patients and
showed that VAP patients had significantly lower levels of IL-17A in the
endotracheal aspirate compared to patients entering ICU with pre-existing
pneumonia. These translational data, obtained both in animal models and in
humans, suggest that a deficient anti-bacterial Th17 response in the lung during
MV is associated with VAP development.

DOI: 10.3390/ijms20205072
PMCID: PMC6829394
PMID: 31614857 [Indexed for MEDLINE]

Conflict of interest statement: O.A. and A.R. are employees of AstraZeneca. The
other authors declare no conflict of interest.


63. Rhinology. 2019 Feb 1;57(1):57-66. doi: 10.4193/Rhin18.131.

Impact of cigarette smoke and IL-17A activation on asthmatic patients with
chronic rhinosinusitis.

Huang CC(1)(2), Lee TJ(1)(3), Huang CC(1)(2), Chang PH(1)(2), Fu CH(1)(2), Wu
PW(1)(4), Wang CH(5).

Author information:
(1)Division of Rhinology, Department of Otolaryngology, Chang Gung Memorial
Hospital and Chang Gung University, Taoyuan, Taiwan.
(2)Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang
Gung University, Taiwan.
(3)Department of Otolaryngology, Xiamen Chang Gung Hospital, Xiamen, China.
(4)Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial
Hospital and Chang Gung University, Keelung, Taiwa.
(5)Department of Thoracic Medicine, Chang Gung Memorial Hospital and Medicine of
College, Chang Gung University, Taoyuan, Taiwan.

Background: Cigarette smoke have adverse effects in the control of asthma and
chronic rhinosinusitis (CRS). Interleukin (IL)-17A, the signature cytokine of
helper T 17 cells and group 3 innate lymphoid cells (ILC3), has been reported to
link with resistance to therapy in airway inflammation. This study aimed to
investigate the impact of cigarette smoking and IL-17A activation on the
clinical outcomes of asthmatic patients with chronic rhinosinusitis. Methods: 33
patients with CRS and asthma, including 15 smokers and 18 non-smokers, and 7
asthmatic patients without CRS and smoking were prospectively recruited. The
Sino-Nasal Outcome Test-22 and Asthma Control Test were used to evaluate
sinonasal symptoms and the level of asthma control, respectively. Real-time PCR
and immunostaining were applied to evaluate the expression levels of IL-17A and
associated immunological factors on surgically-obtained nasal tissues. Results:
Nasal surgery improved both sinonasal symptoms and asthma control. Compared to
non-smokers, smokers showed poorer improvement in asthma control. The expression
of IL-17A, IL-22, aryl hydrocarbon receptor (AhR), and ILC3 was increased in the
nasal tissues of smokers with asthma and CRS. The expression of IL-17A mRNA was
correlated with that of AhR and with positive nuclear AhR-AhR nuclear
translocator staining cells, and that of cyclooxygenase-2 enzyme (COX-2). ILC3
cells were associated with IL-17A, IL-22, AhR, and COX-2 mRNA expression.
Conclusions: Cigarette smoking was related to lesser improvement in asthma
control after nasal surgery and to IL-17A activation in the nasal tissues of
patients with inflammatory airways.

DOI: 10.4193/Rhin18.131
PMID: 30609423 [Indexed for MEDLINE]


64. Arch Immunol Ther Exp (Warsz). 2015 Dec;63(6):435-49. doi:
10.1007/s00005-015-0344-z. Epub 2015 Jun 11.

The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases.

Tabarkiewicz J(1), Pogoda K(2), Karczmarczyk A(3), Pozarowski P(4), Giannopoulos
K(3).

Author information:
(1)Centre for Innovative Research in Medical and Natural Sciences, Medical
Faculty, University of Rzeszów, Rzeszow, Poland. jacek.tabarkiewicz@gmail.com.
(2)Centre for Innovative Research in Medical and Natural Sciences, Medical
Faculty, University of Rzeszów, Rzeszow, Poland.
(3)Department of Experimental Hematooncology, Medical University of Lublin,
Lublin, Poland.
(4)Department of Clinical Immunology, Medical University of Lublin, Lublin,
Poland.

The end of twentieth century has introduced some changes into T helper (Th)
cells division. The identification of the new subpopulation of T helper cells
producing IL-17 modified model of Th1-Th2 paradigm and it was named Th17. High
abilities to stimulate acute and chronic inflammation made these cells ideal
candidate for crucial player in development of autoimmune disorders. Numerous
publications based on animal and human models confirmed their pivotal role in
pathogenesis of human systemic and organ-specific autoimmune diseases. These
findings made Th17 cells and pathways regulating their development and function
a good target for therapy. Therapies based on inhibition of Th17-dependent
pathways are associated with clinical benefits, but on the other hand are
frequently inducing adverse effects. In this review, we attempt to summarize
researches focused on the importance of Th17 cells in development of human
autoimmune diseases as well as effectiveness of targeting IL-17 and its pathways
in pre-clinical and clinical studies.

DOI: 10.1007/s00005-015-0344-z
PMCID: PMC4633446
PMID: 26062902 [Indexed for MEDLINE]


65. Exp Dermatol. 2017 Apr;26(4):305-311. doi: 10.1111/exd.13067. Epub 2017 Feb 27.

Sexy again: the renaissance of neutrophils in psoriasis.

Schön MP(1), Broekaert SM(1), Erpenbeck L(1).

Author information:
(1)Department of Dermatology, Venereology and Allergolosgy, University Medical
Center Göttingen, Göttingen, Germany.

Comment in
    Exp Dermatol. 2017 Apr;26(4):312-313.

Notwithstanding their prominent presence in psoriatic skin, the functional role
of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by
exciting scientific discoveries regarding neutrophil functions within the last
years, the interest in these short-lived cells of the innate immune system has
been boosted recently. While it had been known for some time that neutrophils
produce and respond to a number of inflammatory mediators, recent research has
linked neutrophils with the pathogenic functions of IL-17, possibly in
conjunction with the formation of NETs (neutrophil extracellular traps).
Antipsoriatic therapies exert their effects, at least in part, through
interference with neutrophils. Neutrophils also appear to connect psoriasis with
comorbid diseases. However, directly tampering with neutrophil functions is not
trivial as evinced by the failure of therapeutic approaches targeting
redundantly regulated cellular communication networks. It has also become
apparent that neutrophils link important pathogenic functions of the innate and
the adaptive immune system and that they are intricately involved in regulatory
networks underlying the pathophysiology of psoriasis. In order to advocate
intensified research into the role of this interesting cell population, we here
highlight some features of neutrophils and put them into perspective with our
current view of the pathophysiology of psoriasis.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOI: 10.1111/exd.13067
PMID: 27194625 [Indexed for MEDLINE]


66. Roum Arch Microbiol Immunol. 2011 Jul-Sep;70(3):124-8.

Is interleukin-17 a proatherogenic biomarker?

Cătană CS(1), Cristea V, Miron N, Neagoe IB.

Author information:
(1)Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, România.
kristymed@yahoo.com

The importance of chronic inflammation in atherogenesis and cytokine involvement
in all stages of atherosclerotic plaque development is now obvious. Our approach
of the significant cytokines involved in atherogenesis or cardiovascular
diseases is based on a correlation between clinical research and experiments on
animal models. The contribution of IL-17 in atherogenesis remains controversial.
In this study we investigated the role of IL-17 in cardiovascular diseases and
in atherosclerosis associated with pathological aging. We performed a
case-control study, enrolling subjects aged over 65 years in both groups. We
included 40 patients with cardiovascular disorders and 10 healthy volunteers.
IL-17 levels were measured in the serum of patients and healthy controls, along
with serum total cholesterol and triglycerides. Significantly higher levels of
IL-17 were obtained in patients compared to healthy controls (p<0.001). The
level of this biomarker correlated significantly with two biochemical parameters
- serum total cholesterol and triglycerides (the Pearson coefficient showed
statistical significance, p=0.033, respectively p=0.043). We did not find any
correlation between IL-17 and these two parameters in the control group. Our
study is useful in understanding the physiopathological implications of IL-17 in
the atherogenesis process. This could represent a starting point for future
studies, including research regarding the therapeutic potential of IL-17 in
pathological aging.

PMID: 22570926 [Indexed for MEDLINE]


67. Zhonghua Kou Qiang Yi Xue Za Zhi. 2017 Dec 9;52(12):740-747. doi:
10.3760/cma.j.issn.1002-0098.2017.12.006.

[Effects of T helper 1 cells and T helper 17 cells secreting cytokines on rat
models of experimental periodontitis].

[Article in Chinese; Abstract available in Chinese from the publisher]

Wang ZX(1), Yang L(1), Tan JY(1), Chen LL(1).

Author information:
(1)Department of Periodontology, The Second Affiliated Hospital of Zhejiang
University School of Medicine, Hangzhou 310009, China.

Objectvie: To investigate the effects of secreting cytokines interferon-gamma
(IFN-γ) and interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17
cells (Th17) on the peripheral blood and alveolar bone destruction, so as to
provide a new explanation for cellular immunity-mediated alveolar bone
destruction. Methods: Eighteen eight-week-old male Sprague-Dawley rats were
divided, randomly and equally, into 3 groups: lipopolysaccharide (LPS) group,
ligation group and normal control group. In the LPS group, Escherichia coli LPS
was injected into the alveolar mucosa on the buccalmedian site of the left upper
first molar, while the right upper first molar was injected with equal volume of
physiological saline as self-controls. The injections were performed every other
day for four times totally. In the ligation group, the left upper first molars
were ligatured with 0.2 mm orthodontic cords, while the right upper first molars
were left untreated as self-controls, and supplemented with high-sugar diet to
promote the periodontitis status. The rats in normal control group were fed
normally. The concentrations of IFN-γ and IL-17 in peripheral blood were
measured using enzyme linked immunosorbent assay (ELISA) method at the fourth
week after the start of injection and at the eighth week after ligation. The
histological of periodontal tissues were observed after hematoxylin-eosin (HE)
staining and osteoclast count was performed under light microscope. The
histological of osteoclasts were observed after tartrate-resistant acid
phosphatase (TRAP) staining. Expression of IFN-γ and IL-17 were detected by
immunohistochemical assay. Results: The concentrations of IFN-γ in peripheral
blood of LPS group [(185.0±50.7) ng/L] and ligation group [(202.9±60.4) ng/L]
were significantly higher than that of normal control group [(106.3±17.2)
ng/L](P<0.05). Meanwhile, histological examination showed inflammatory cells
infiltration in the gingival epithelium, the height reduction of alveolar bone
accompanied with absorption lacuna. There were significantly higher HE and TRAP
stained osteoclasts in LPS group (9.50±1.05) and ligation group (10.83±1.17)
than that in controlgroup (0.33±0.52)(P<0.05). Moreover, the expressions of
IL-17 in alveolar bone absorption area of LPS group and ligation group were
significantly stronger than that in control group (P<0.05). Conclusions: The rat
models of experimental periodontitis and alveolar bone resorption could be
successfully established by means of ligationand LPS injection, respectively.
The periodontal inflammatory responses were related to secreting cytokines IFN-γ
and IL-17 of Th1 and Th17 cells, while Th17 cells might exert a positive effect
on alveolar bone destruction.

Publisher: 目的：
探究辅助性T细胞1和17特征性分泌因子干扰素γ和白细胞介素17（interleukin-17，IL-17）在实验性大鼠牙周炎外周血和牙槽骨破坏区域的表达差异，为细胞免疫介导的牙槽骨破坏提供理论依据。
方法：
选择8周龄健康雄性SD大鼠18只，按随机数字表法随机分为3组：大肠杆菌内毒素脂多糖（lipopolysaccharide，LPS）组、结扎组和正常对照组，每组6只。LPS组大鼠采用上颌第一磨牙颊侧隔天注射LPS的方法建立实验性牙周炎模型，共注射4次；结扎组大鼠采用0.2
mm正畸丝结扎上颌第一磨牙并辅以高糖饮食；正常对照组大鼠不做任何处理，正常喂养。分别于注射后第4周、结扎后第8周处死动物，采用酶联免疫吸附测定法检测大鼠外周血清中干扰素γ和IL-17的含量；HE染色观察各组大鼠牙周组织变化并于光镜下进行破骨细胞计数；抗酒石酸酸性磷酸酶（tartrate-resistant
acid phosphatase，TRAP）染色观察牙槽骨组织内破骨细胞情况；免疫组化法检测牙周局部组织中干扰素γ和IL-17的表达。 结果：
LPS组和结扎组大鼠外周血清干扰素-γ的表达[分别为（185.0±50.7）、（202.9±60.4）ng/L]均显著高于对照组[（106.3±17.2）ng/L]（P<0.05）；HE染色可见LPS组和结扎组大鼠的牙龈上皮内有不同程度的炎性细胞浸润，牙槽骨高度降低，出现骨吸收陷窝，且LPS组和结扎组破骨细胞计数[分别为（9.05±1.05）、（10.83±1.17）个]均较对照组[（0.33±0.52）个]显著增加（P<0.05）；TRAP染色显示LPS组和结扎组可见大量体积较大、胞质红染、内有蓝色核仁的多核破骨细胞；此外，LPS组和结扎组大鼠牙槽骨吸收区域IL-17的表达显著高于对照组。
结论：
采用LPS定点注射法可建立大鼠牙槽骨吸收模型，结扎法可成功建立大鼠实验性牙周炎模型；干扰素γ和IL-17均参与牙周炎发生过程，IL-17可能与牙槽骨吸收破坏有关。.

DOI: 10.3760/cma.j.issn.1002-0098.2017.12.006
PMID: 29275568 [Indexed for MEDLINE]


68. Immunity. 2012 Apr 20;36(4):668-79. doi: 10.1016/j.immuni.2012.02.013. Epub 2012
Mar 29.

Prostaglandin E2 suppresses antifungal immunity by inhibiting interferon
regulatory factor 4 function and interleukin-17 expression in T cells.

Valdez PA(1), Vithayathil PJ, Janelsins BM, Shaffer AL, Williamson PR, Datta SK.

Author information:
(1)Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases,
National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, MD 20892, USA.

T helper 17 (Th17) cells play an important role in mucosal host defense through
production of the signature cytokines IL-17 and IL-22. Prostaglandin E2 (PGE2)
has been shown to enhance IL-17 production by mature Th17 cells. However, when
present during Th17 cell differentiation, we found that PGE2 inhibited the
transcription factor IRF4 and suppressed production of IL-17 but not IL-22. We
show that IRF4 was required for IL-17 expression but inhibited IL-22 expression,
highlighting the potential for discordant regulation of these two cytokines in
Th17 cells. The pathogenic fungus Cryptococcus neoformans produces PGE2, and we
found that it uses PGE2- and IRF4-dependent mechanisms to specifically inhibit
induction of IL-17 during Th17 cell differentiation. Blockade of host PGE2
during infection led to increased IL-17 production from CD4(+) T cells and
increased survival of mice. These findings suggest that host- or
pathogen-derived PGE2 can act directly on Th17 cells during differentiation to
inhibit IL-17-dependent antimicrobial responses.

Copyright © 2012 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.immuni.2012.02.013
PMCID: PMC3334441
PMID: 22464170 [Indexed for MEDLINE]


69. PLoS One. 2014 Sep 8;9(9):e106834. doi: 10.1371/journal.pone.0106834.
eCollection 2014.

Intratumor IL-17-positive mast cells are the major source of the IL-17 that is
predictive of survival in gastric cancer patients.

Liu X(1), Jin H(1), Zhang G(1), Lin X(1), Chen C(1), Sun J(1), Zhang Y(1), Zhang
Q(1), Yu J(1).

Author information:
(1)Department of Gastrointestinal Surgery, the First Affiliated Hospital,
Medical College, Zhejiang University, Hangzhou, China.

Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective
anti-tumor immune responses. However, the source of the increased
tumor-infiltrating IL-17 and its contribution to tumor progression in human
gastric cancer remain poorly understood. In this study, we enrolled 112 gastric
cancer patients, immunofluorescence was used to evaluate the colocalization of
CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17.
Immunohistochemistry was used to evaluate the distribution of microvessel
density (CD34), CD66b(+), CD68(+), and FoxP3(+) cells in different
microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis
and a Cox regression model. The results showed that mast cells, but not T cells
or macrophages, were the predominant cell type producing IL-17 in gastric
cancer. Significant positive correlations were detected between densities of
mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells
(Tregs). Furthermore, we found that the majority of vascular endothelial cells
expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that
increasing intratumor infiltrated mast cells and IL-17(+) cells, as well as
MCT(+) IL-17(+) cells, were significantly associated with worse overall
survival. These findings indicated that mast cells were the major source of
IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted
tumor progression by enhancing angiogenesis in the tumor microenvironment
through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic
factor in gastric cancer, indicating that immunotherapy targeting mast cells
might be an effective strategy to control intratumor IL-17 infiltration, and
consequently reverse immunosuppression in the tumor microenvironment,
facilitating cancer immunotherapy.

DOI: 10.1371/journal.pone.0106834
PMCID: PMC4157802
PMID: 25197971 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: The authors have declared
that no competing interests exist.


70. Protein Cell. 2011 Jan;2(1):26-40. doi: 10.1007/s13238-011-1006-5. Epub 2011 Feb
20.

Structure and function of interleukin-17 family cytokines.

Zhang X(1), Angkasekwinai P, Dong C, Tang H.

Author information:
(1)Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

The recently identified interleukin-17 (IL-17) cytokines family, which comprises
six members in mammals (IL-17A-F), plays essential roles in the host immunity
against infectious diseases and chronic inflammatory diseases. The
three-dimensional structures containing IL-17A or IL-17F have become available
and revealed the unique structural features of IL-17s as well as their
receptors. Molecular modeling in this review shows that IL-17s may adopt a
"cysteine knot" fold commonly seen in nerve growth factor (NGF) and other
neurotrophins. Further modeling analysis unmasks a signature interaction feature
of the IL-17F/IL-17RA complex, where a small loop of IL-17RA slots into the deep
groove of the interface of IL-17F homodimer. This is quite different from the
interaction between the best known four-helix cytokines and their cognate
receptors. On the other hand, structure of IL-17A and its monoclonal antibody
(CAT-2200) shows that, albeit that the antigenic epitope of IL-17A resides
outside of the IL-17A homodimer interface, its physical proximity to the
receptor binding groove may explain that antibody blockage would be achieved by
interfering with the ligand-receptor interaction. This review is to summarize
the advance in understanding the structure and function of IL-17 family
cytokines, focusing mainly on IL-17A, IL-17F and IL-17E, in the hope of gaining
better knowledge of immunotherapeutic strategies against various inflammatory
diseases.

DOI: 10.1007/s13238-011-1006-5
PMCID: PMC4875287
PMID: 21337007 [Indexed for MEDLINE]


71. Nat Commun. 2014 Jun 9;5:3986. doi: 10.1038/ncomms4986.

Differential developmental requirement and peripheral regulation for dermal Vγ4
and Vγ6T17 cells in health and inflammation.

Cai Y(1), Xue F(2), Fleming C(3), Yang J(4), Ding C(3), Ma Y(3), Liu M(3), Zhang
HG(3), Zheng J(5), Xiong N(4), Yan J(3).

Author information:
(1)1] James Graham Brown Cancer Center, Department of Medicine and Department of
Microbiology and Immunology, University of Louisville, Louisville, Kentucky
40202, USA [2].
(2)1] Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai
Jiaotong University, Shanghai 200025, China [2].
(3)James Graham Brown Cancer Center, Department of Medicine and Department of
Microbiology and Immunology, University of Louisville, Louisville, Kentucky
40202, USA.
(4)Center for Molecular Immunology and Infectious Diseases and Department of
Veterinary and Biomedical Sciences, Pennsylvania State University, University
Park, Pennsylvania 16802, USA.
(5)Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai
Jiaotong University, Shanghai 200025, China.

Erratum in
    Nat Commun. 2016;7:11354.

Dermal IL-17-producing γδT cells have a critical role in skin inflammation.
However, their development and peripheral regulation have not been fully
elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic
thymus and undergo homeostatic proliferation after birth with diversified TCR
repertoire. Vγ6T cells are bona fide resident, but precursors of dermal Vγ4T
cells may require extrathymic environment for imprinting skin-homing properties.
Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell
reconstitution and TCRδ(-/-) mice reconstituted with Vγ6 develop psoriasis-like
inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4
and Vγ6 proliferation, Vγ4 are the main source of IL-17 production that requires
IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly
decreased skin inflammation. These studies reveal a differential developmental
requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying
a new mechanism that may be involved in skin inflammation.

DOI: 10.1038/ncomms4986
PMCID: PMC4068267
PMID: 24909159 [Indexed for MEDLINE]


72. Fa Yi Xue Za Zhi. 2016 Feb;32(1):40-4.

[Correlation between Expression of Peripheral IL-17 Protein and Aggression of
Bipolar Mania].

[Article in Chinese]

Li HZ, Hong W, Wang ZW, Yuan CM, Li ZZ, Huang J, Zhang C, Li NN, Lin ZG, Fang
YR.

OBJECTIVE: To explore the correlation between the interleukin-17 (IL-17) level
of peripheral blood and aggression of bipolar mania.
METHODS: Thirty-six patients of bipolar mania were selected as experimental
group by DSM-IV-TR and received treatment with quetiapine and lithium.
Thirty-six healthy volunteers with similar age and gender were selected as
control group. The level of IL-17 at baseline in each group and the level of
IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were
detected by ELISA.
RESULTS: The level of IL-17 in experimental group at baseline, after treatment
for 2 and 4 weeks were all significantly higher than that in control group.
After 8 weeks treatment, there was no significant difference between the two
groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and
aggression score of Young Mania Rating Score (YMRS) were significantly lower
than the baseline level (P < 0.05). In experimental group, the level of IL-17
was positively correlated with the two scores of YMRS at baseline (P < 0.05).
CONCLUSION: Bipolar mania may be related to the up-regulation of IL-17. The
level of IL-17 is related to the severity of manic symptoms at baseline,
especially aggression symptom.

PMID: 27295856 [Indexed for MEDLINE]


73. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2005 Dec;40(12):899-902.

[Expression and significance of interleukin-17 and its receptor in nasal
polyps].

[Article in Chinese]

Wang X(1), Dong Z.

Author information:
(1)Department of Otorhinolaryngology Head and Neck Surgery, China-Japan
Friendship Hospital, Jilin University, Changchun.

OBJECTIVE: To detect the expression and distribution of interleukin-17 and
interleukin 17 receptor (IL-17R) in nasal polyps and to probe into their
significance in the pathology of nasal polyps.
METHODS: The methods of immunohistochemical staining and western blot were used
to detect IL-17 and IL-17R in nasal polyps and controls.
RESULTS: In nasal polyp tissues, IL-17 expressed mainly in cytoplasm of plasm
cell, less in prickle-cell layer of the epithelium and the acinus of the serous
gland. In turbinates, IL-17 also expressed in the cytoplasm of the plasm cell,
the prickle-cell layer of the epithelium and the acinus of the serous gland. The
expression of IL-17 between nasal polyps and turbinates differed significantly
(t = 2.237, 2.176, 2.246, P < 0.05, respectively). Both IL-17 and IL-17R
displayed specific bands in nasal polyps and turbinates, but the bands of IL-17
and IL-17R in nasal polyps were stronger than those in turbinates.
CONCLUSIONS: IL-17 may have an important role in the occurrence of nasal polyps
by specific combination with IL-17R and over-expression in nasal polyps.

PMID: 16874957 [Indexed for MEDLINE]


74. Br J Dermatol. 2017 Nov;177(5):1458-1460. doi: 10.1111/bjd.15358. Epub 2017 Aug
16.

IL-17A localizes in the exocytic compartment of mast cells in psoriatic skin.

Brembilla NC(1), Stalder R(1), Senra L(1), Boehncke WH(1)(2).

Author information:
(1)Department of Pathology and Immunology, University of Geneva, Geneva,
Switzerland.
(2)Division of Dermatology and Venereology, Geneva University Hospitals and
School of Medicine, Geneva, Switzerland.

DOI: 10.1111/bjd.15358
PMID: 28144966 [Indexed for MEDLINE]


75. J Mol Neurosci. 2019 Feb;67(2):217-226. doi: 10.1007/s12031-018-1227-7. Epub
2018 Nov 27.

Non-invasive Vagus Nerve Stimulation Protects Against Cerebral
Ischemia/Reperfusion Injury and Promotes Microglial M2 Polarization Via
Interleukin-17A Inhibition.

Zhao XP(1), Zhao Y(2), Qin XY(3), Wan LY(3), Fan XX(4).

Author information:
(1)Department of Neurosurgery, Affiliated Hospital of Shaanxi University of
Chinese Medicine, Xianyang, 712000, China.
(2)College of foreign languages, Shaanxi University of Chinese Medicine,
Xianyang, 712046, China.
(3)First Clinical Medical College of Shaanxi University of Chinese Medicine,
Xianyang, 712046, China.
(4)Department of Neurosurgery, Affiliated Hospital of Shaanxi University of
Chinese Medicine, Xianyang, 712000, China. fanxiaoxuanedu@126.com.

Microglia play an essential role during cerebral an ischemia/reperfusion
(I/R)-related inflammatory process. Because the M2 phenotype of microglia
exhibits anti-inflammation activity, it has become a promising target for
anti-inflammatory therapy. Vagus nerve stimulation (VNS) reportedly has
neuroprotective effects against cerebral I/R injuries via its anti-inflammatory
action. The aim of this study was to investigate the ability of non-invasive VNS
(nVNS) to alleviate cerebral I/R in mice by promoting microglial M2
polarization. Neurological scoring and cerebral infarct volume assessments were
performed 72 h after a middle cerebral artery occlusion (MCAO)-induced stroke.
M2 phenotype microglia were identified by immunohistochemistry staining using
Arg-1 and Iba-1 antibodies. The protein expressions of Arg-1, IL-17A, IL-10,
Bax, and Bcl-2 were detected by Western blot. Apoptotic cells were detected
using TUNEL staining. According to our results, nVNS decreased infarct volume,
improved neurological outcomes, reduced apoptotic neurons (TUNEL+NeuN+ cells),
and promoted microglial M2 polarization as indicated by elevated Arg-1 protein
expression and increased Arg-1+ cells after MCAO. Moreover, nVNS attenuated the
increased levels of IL-17A protein expression after MCAO. To test the possible
involvement of IL-17A in nVNS-induced neuroprotection and microglial M2
polarization, 1-μg recombinant IL-17A (rIL-17A) was intranasally administered
once daily for three consecutive days after reperfusion. We found that the
intranasal administration of rIL-17A nullified the nVNS-induced promotion of
microglial M2 polarization. Furthermore, rIL-17A administration abolished the
neuroprotective effect of nVNS. In conclusion, our study identifies microglial
M2 polarization as an important mechanism underlying the nVNS-mediated
neuroprotection against cerebral I/R. This effect of nVNS could be attributed to
the inhibition of IL-17A expression.

DOI: 10.1007/s12031-018-1227-7
PMID: 30484061 [Indexed for MEDLINE]


76. Clin Exp Dermatol. 2011 Apr;36(3):292-7. doi: 10.1111/j.1365-2230.2010.03972.x.
Epub 2010 Dec 24.

Role of interleukin-17 in the pathogenesis of vitiligo.

Bassiouny DA(1), Shaker O.

Author information:
(1)Department of Dermatology, Kasr El-Aini University Hospital, Cairo
University, Cairo, Egypt. daliabas73@yahoo.com

BACKGROUND: Skewing of the immune response towards T helper (Th)1 or Th17 and
away from regulatory T cells (Tregs) and Th2 cells may be responsible for the
development and progression of autoimmune disease. An autoimmune theory has been
proposed in the pathogenesis of vitiligo. No previous reports have investigated
alterations in IL-17 produced by Th17 cells in lesional skin in vitiligo.
AIM: To investigate the role of IL-17 in the pathogenesis of vitiligo by
assessing its levels in lesional skin and serum of patients with vitiligo
compared with controls.
METHODS: In total, 30 patients with vitiligo and 20 controls matched for age and
gender were enrolled in the study. Serum and tissue IL-17 levels were measured
by ELISA and compared between both groups for correlations with age, gender,
family history, disease duration, activity of vitiligo and percentage of
involved body surface area.
RESULTS: A significant difference between patients and healthy controls was
found for both serum and tissue IL-17 levels (P<0.001 for both). Significant
positive correlations were found between disease duration and IL-17 level in
both serum (r=0.42, P=0.02) and lesional skin (r=0.45, P<0.015); between extent
of vitiligo and IL-17 levels in both serum (r=0.65, P<0.001) and skin (r=0.48,
P<0.05); and between the serum and the tissue IL-17 levels in patients with
vitiligo (r=0.54, P=0.002).
CONCLUSIONS: Multiple factors have been implicated in the pathogenesis of
vitiligo. The increased levels of IL-17 we found in serum and lesional skin
suggest an important role for this cytokine in the pathogenesis of vitiligo.

© The Author(s). CED © 2010 British Association of Dermatologists.

DOI: 10.1111/j.1365-2230.2010.03972.x
PMID: 21198791 [Indexed for MEDLINE]


77. J Neuroimmunol. 2016 Mar 15;292:79-80. doi: 10.1016/j.jneuroim.2016.01.017. Epub
2016 Jan 27.

Immunomodulation by vitamin D in multiple sclerosis: More than IL-17.

Smolders J(1), Muris AH(2), Damoiseaux J(3).

Author information:
(1)Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The
Netherlands; Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen,
The Netherlands. Electronic address: smolders@gmail.com.
(2)Academic MS Center Limburg, Zuyderland Medical Center, Sittard, The
Netherlands; School For Mental Health & Neuroscience, Maastricht University
Medical Center, Maastricht, The Netherlands.
(3)Central Diagnostic Laboratory, Maastricht University Medical Center,
Maastricht, The Netherlands.

Comment on
    J Neuroimmunol. 2015 Aug 15;285:125-8.

DOI: 10.1016/j.jneuroim.2016.01.017
PMID: 26943962 [Indexed for MEDLINE]


78. BMC Res Notes. 2017 Jun 12;10(1):202. doi: 10.1186/s13104-017-2517-9.

Expression of mRNA IL-17F and sIL-17F in atopic asthma patients.

Hatta M(1), Surachmanto EE(2), Islam AA(3), Wahid S(4).

Author information:
(1)Molecular Biology and Immunology Laboratory, Faculty of Medicine, Hasanuddin
University, Makassar, Indonesia. hattaram@indosat.net.id.
(2)Allergy Immunology Division, Department of Internal Medicine, Faculty of
Medicine, Sam Ratulangi University, Manado, Indonesia.
(3)Department of Neurosurgery, Faculty of Medicine, Hasanuddin University,
Makassar, Indonesia.
(4)Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University,
Makassar, Indonesia.

BACKGROUND: Asthma is a chronic inflammatory disorder of airway that involves
many cells and elements. Chronic inflammation caused by increase Airway
hyperresponsiveness that cause recurrent episodic symptoms of breathlessness,
wheezing, chest tightness and coughing, especially at night or early morning.
Interleukin 17F is a cytokine that plays an important role in the
pathophysiology of asthma attacks. Some studies show a variety of IL-17F roles
in the pathogenesis of airway inflammation due to an allergic reaction.
RESULTS: The study was conducted at the Prof. Dr. R. D. Kandou Manado Hospital,
Indonesia. Samples were taken continuously until the number of meant samples was
achieved. Blood samples were collected from 40 atopic asthmatic patients. From
statistical analysis based on the hypothesis, there was positive correlation
between mRNA levels of IL-17F and IL-17F in atopic asthmatic patient (p = 0.000
and r = 0.988).
CONCLUSIONS: According these data suggest that levels of mRNA IL-17F and IL17F
might be useful parameters for the diagnosis of atopic asthma patient.

DOI: 10.1186/s13104-017-2517-9
PMCID: PMC5469059
PMID: 28606156 [Indexed for MEDLINE]


79. J Periodontol. 2016 Dec;87(12):1484-1491. doi: 10.1902/jop.2016.160146. Epub
2016 Aug 19.

Salivary Concentrations of Interleukin (IL)-1β, IL-17A, and IL-23 Vary in
Relation to Periodontal Status.

Liukkonen J(1), Gürsoy UK(1), Pussinen PJ(2), Suominen AL(3)(4)(5), Könönen
E(1)(6).

Author information:
(1)Department of Periodontology, Institute of Dentistry, University of Turku,
Turku, Finland.
(2)Department of Oral and Maxillofacial Diseases, University of Helsinki,
Helsinki, Finland.
(3)Unit of Living Conditions, Health and Wellbeing, and Department of
Environmental Health in Environmental Epidemiology Unit, National Institute for
Health and Welfare, Helsinki, Finland.
(4)Institute of Dentistry, University of Eastern Finland, Kuopio, Finland.
(5)Department of Oral and Maxillofacial Surgery, Kuopio University Hospital,
Kuopio, Finland.
(6)Oral Health Care, Welfare Division, City of Turku, Turku, Finland.

BACKGROUND: Interleukin (IL)-23-induced T helper (Th) 17 pathway is involved in
the pathogenesis of periodontal disease. This study's aim is to determine levels
of IL-1β, IL-17A, IL-23, and lipopolysaccharide (LPS) in saliva, and to examine
whether their salivary concentrations are associated with periodontal health
status.
METHODS: Saliva samples originated from 220 participants; 76 had generalized
periodontitis (GP) and 65 had localized periodontitis (LP), whereas 79 without
periodontitis were used as controls. Cytokine analyses were performed by a flow
cytometry-based technique and LPS analyses from pellet by commercially optimized
assay coupled with chromogenic substrate.
RESULTS: Salivary concentrations of IL-17A and IL-23 were elevated significantly
in patients with LP compared with controls and patients with GP. Salivary IL-1β
concentrations were significantly higher in patients with GP than in patients
with LP, whereas no difference was found between LP and control groups.
Significant correlation was found between concentrations of IL-17A and IL-23 or
IL-1β. LPS concentrations did not have significant associations with any of the
tested ILs.
CONCLUSION: Elevated salivary IL-1β concentrations are related to GP, whereas
distinct elevation and reduction profiles of IL-17A and IL-23 are detected in
saliva of patients with LP and GP.

DOI: 10.1902/jop.2016.160146
PMID: 27541079 [Indexed for MEDLINE]


80. Bull Exp Biol Med. 2019 Mar;166(5):622-625. doi: 10.1007/s10517-019-04405-3.
Epub 2019 Mar 22.

Cytokine Profiling of Subclinical Tick-Borne Infections in Humans.

Danchinova GA(1), Khasnatinov MA(2), Lyapunova NA(2), Solovarov IS(2), Manzarova
EL(2), Lyapunov AV(2), Petrova IV(2).

Author information:
(1)Research Center for Family Health and Human Reproduction Problems, Irkutsk,
Russia. dan-chin@yandex.ru.
(2)Research Center for Family Health and Human Reproduction Problems, Irkutsk,
Russia.

Over many years, tick-borne infections remain one of the most serious threats to
human health worldwide. The immune response to these infections in a human after
confirmed bite by an infected carrier at the early stages of infection in the
absence of clinical symptoms can be the first indicator of the presence of the
infectious agent in the body. During viral infection, the concentration of
IL-1α, IL-8, IL-10, IL-17A, and IFNγ increases; superoxide dismutase also
increases, in contrast to bacterial infections. A slight decrease in the
concentration is observed only for receptor antagonist IL-1Ra. During the
infection caused by bacterial pathogens, very similar profiles of the innate
human immune response are observed: activation of IL-1α, IL-8, and IFNα and
suppression of superoxide dismutase, IL-1Ra, and IL-17A production. It has been
demonstrated, that the immune response is triggered immediately after infection,
and changes in the concentration of the main cytokines in the blood plasma can
be detected as early as on days 2-5 after tick bite. These results can be useful
in developing new methods of emergency diagnosis and prevention of tick-borne
infections.

DOI: 10.1007/s10517-019-04405-3
PMID: 30903500 [Indexed for MEDLINE]


81. Genet Mol Res. 2015 Mar 27;14(1):2413-21. doi: 10.4238/2015.March.27.26.

Detection of targets and their mechanisms for early diagnosis of traumatic deep
vein thrombosis.

Mo JW(1), Zhang DF(2), Ji GL(2), Liu XZ(2), Fan B(2).

Author information:
(1)Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan
Medical University, Ganzhou, Jiangxi Province, China BinFan20149@163.com.
(2)Department of Orthopedic Surgery, The First Affiliated Hospital of Gannan
Medical University, Ganzhou, Jiangxi Province, China.

The purpose of this investigation was to identify targets for the early
diagnosis and predictors of deep venous thrombosis (DVT) and the role of these
targets in the formation of venous thrombosis. A model of DVT was constructed in
rats. Thromboses and venous walls were sampled for reverse transcription
polymerase chain reaction study, and blood was sampled for enzyme-linked
immunosorbent assay studies. Vein endothelial cells were cultured to observe the
effects of interleukin (IL)-17 on the expression of tissue plasminogen activator
(t-PA)/plasminogen activator inhibitor type 1 (PAI-1). IL-17 monoclonal antibody
was used to study its effect on preventing the formation of DVT. One-hundred and
twenty hours after the animal model was constructed, significant DVT started to
form. Polymerase chain reaction tests showed that immediately after the model
was created, the expression of IL-17 increased greatly, whereas the balance
between t-PA and PAI-1 was disrupted just before DVT formed. The increase of
serum IL-17 was positively related with the formation of DVT. Thus, the
application of IL-17 monoclonal antibody could reduce the formation of DVT in
rats. IL-17 might be a target for the early diagnosis of DVT and should be
further studied to assess its clinical value.

DOI: 10.4238/2015.March.27.26
PMID: 25867387 [Indexed for MEDLINE]


82. Neurosci Lett. 2011 Apr 15;493(3):86-91. doi: 10.1016/j.neulet.2011.01.079. Epub
2011 Feb 21.

Interleukin-17 levels in rat models of nerve damage and neuropathic pain.

Noma N(1), Khan J, Chen IF, Markman S, Benoliel R, Hadlaq E, Imamura Y, Eliav E.

Author information:
(1)Department of Diagnostic Sciences, Division of Orofacial Pain, New Jersey
Dental School, University of Medicine and Dentistry in New Jersey, 110 Bergen
Street, Newark, NJ, United States. noma@dent.nihon-u.ac.jp

In the present study, we assessed IL-17 levels at 3 and 8 days following various
forms of injuries to the sciatic nerve and related the cytokine levels to the
pain behaviors associated with the injuries. The four experimental models
employed were chronic constriction injury (CCI), partial sciatic ligation (PSL),
complete sciatic transection (CST) and perineural inflammation (Neuritis).
Behavior withdrawal thresholds for mechanical stimulus and withdrawal latency
for thermal stimulation were used to measure mechanical allodynia and thermal
hyperalgesia. IL-17 levels of the affected, contralateral and naïve rats'
sciatic nerve were assessed employing enzyme-linked immunosorbent assay (ELISA).
Rats exposed to CCI and Neuritis displayed significant mechanical allodynia and
thermal hyperalgesia 3, 5 and 8 days following the procedure, rats exposed to
PSL displayed significant mechanical allodynia 5 and 8 days following the
procedure and rats exposed to CST developed significant hypoesthesia. Three days
following the procedure, IL-17 levels increased significantly compared to naïve
rats only in the PSL model. Eight days following the procedure, IL-17 levels in
nerves exposed to CCI, CST, PSL and Neuritis were significantly elevated compare
to intact nerve levels. It is likely that IL-17 has a limited role in the acute
phase of nerve injury and the associated acute pain, but may have a role in
later phases of the processes of the development of neuropathic pain.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.neulet.2011.01.079
PMID: 21316418 [Indexed for MEDLINE]


83. J Huazhong Univ Sci Technolog Med Sci. 2007 Oct;27(5):498-500. doi:
10.1007/s11596-007-0505-3.

Expression of interleukin-17 in lung and peripheral blood of asthmatic rats and
the influence of dexamethasone.

Xiong W(1), Zeng D, Xu Y, Fang H, Cao Y, Song Q, Cao C.

Author information:
(1)Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College,
Huazhong University of Science and Technology, Wuhan, China.
xiongweining@tjh.tjmu.edu.cn

The expression of interleukin-17 (IL-17) in lung and peripheral blood of
asthmatic rats and the influence of dexamethasone, and the role of IL-17 in the
pathogenesis of asthma were investigated. Thirty Sprague-Dawley (SD) adult rats
were randomly divided into three groups (n=10 in each group): normal group,
asthmatic group, and dexamethasone-interfered group. Rat asthmatic model was
established by intraperitoneal (i.p.) injection of 10% ovalbumin (OVA) and
challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group
were pretreated with dexamethasone (2 mg/kg, i.p.) 30 min before each challenge.
The expression of IL-17 protein in serum and bronchoalveolar lavage fluid (BALF)
was detected by ELISA. The expression of IL-17 mRNA in peripheral blood
mononuclear cells (PBMC) and BALF cells was semi-quantitatively detected by
RT-PCR. The expression of IL-17 protein in serum and BALF of asthmatic rats was
significantly elevated as compared with normal rats and dexamethasone-interfered
rats (P<0.01), and there was significant difference between normal rats and
dexamethasone-interfered rats (P<0.05). The expression of IL-17 mRNA in PBMC and
BALF cells of asthmatic rats was markedly increased as compared with normal rats
and dexamethasone-interfered rats (P<0.01), and significant difference was found
between normal rats and dexamethasone-interfered rats (P<0.05). It was concluded
that the expression of IL-17 was increased significantly in asthmatic rats and
could be inhibited partly by dexamethasone, suggesting that IL-17 might play an
important role in the pathogenesis of asthma as an inflammation regulation
factor.

DOI: 10.1007/s11596-007-0505-3
PMID: 18060619 [Indexed for MEDLINE]


84. Immunol Cell Biol. 2015 Feb;93(2):111-2. doi: 10.1038/icb.2014.111. Epub 2015
Jan 6.

Is DUBA putting the brake on Th17 cells?

Brüstle A(1).

Author information:
(1)Department of Pathogens and Immunity, John Curtin School of Medical Research,
The Australian National University, Canberra, Australia.

Comment on
    Nature. 2015 Feb 19;518(7539):417-21.

DOI: 10.1038/icb.2014.111
PMID: 25559621 [Indexed for MEDLINE]


85. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014 Apr;28(8):516-9.

[Expression and role of IL-17 in nasal polyposis].

[Article in Chinese]

Shen Y, Hong S, Hu G.

OBJECTIVE: To study the expression of interleukin-17 (IL-17) in nasal polyps
from both atopic and nonatopic patients, and its associations with histological
features of polyps tissue.
METHOD: Thirty patients with nasal polyps (NP) were included and divided into
atopic and nonatopic groups according to the skin prick test. Histological
characteristics were assessed by eosinophilic infiltration with HE staining.
IL-17 expression in polyps tissue was detected by ELISA and RT-PCR.
RESULT: Eosinophilic infiltration was significantly higher in atopic NP patients
than in nonatopic NP patients (P < 0.01). IL-17 protein and IL-17 mRNA levels
were significantly upregulated in both atopic (P < 0.01) and nonatopic (P <
0.05) patients compared with controls. Furthermore, IL-17 levels were
significantly higher in the atopic group than in nonatopic group. Significantly
positive correlations were found between IL-17 levels and eosinophilic
infiltration in NP patients.
CONCLUSION: These results indicated that expression of IL-17 was significantly
upregulated in NP patients and was especially higher in atopic NP patients,
suggesting that IL-17 may play an important role in the pathogenesis of NP and
atopy may contribute to NP by stimulating the production of IL-17.

PMID: 25007662 [Indexed for MEDLINE]


86. PLoS One. 2015 Apr 7;10(4):e0122807. doi: 10.1371/journal.pone.0122807.
eCollection 2015.

Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral
and cutaneous candidiasis.

Conti HR(1), Whibley N(1), Coleman BM(1), Garg AV(1), Jaycox JR(2), Gaffen
SL(1).

Author information:
(1)University of Pittsburgh, Department of Medicine, Division of Rheumatology &
Clinical Immunology, Pittsburgh, PA, United States of America.
(2)Carnegie Mellon University, Dept. of Biological Sciences, Pittsburgh, PA,
United States of America.

Candida albicans is a commensal fungal microbe of the human orogastrointestinal
tract and skin. C. albicans causes multiple forms of disease in
immunocompromised patients, including oral, vaginal, dermal and disseminated
candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and
IL-17RC, are required for protection to most forms of candidiasis. The
importance of the IL-17R pathway has been observed not only in knockout mouse
models, but also in humans with rare genetic mutations that impact generation of
Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3
or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of
cytokines is a distinct subclass of cytokines with unique structural and
signaling properties. IL-17A is the best-characterized member of the IL-17
family to date, but far less is known about other IL-17-related cytokines. In
this study, we sought to determine the role of a related IL-17 cytokine, IL-17C,
in protection against oral, dermal and disseminated forms of C. albicans
infection. IL-17C signals through a heterodimeric receptor composed of the
IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following
oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C.
albicans infections in the oral mucosa, skin and bloodstream at rates similar to
WT littermate controls. Moreover, these mice demonstrated similar gene
transcription profiles and recovery kinetics as WT animals. These findings
indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of
candidiasis evaluated, and illustrate a surprisingly limited specificity of the
IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida
infections.

DOI: 10.1371/journal.pone.0122807
PMCID: PMC4388490
PMID: 25849644 [Indexed for MEDLINE]

Conflict of interest statement: Competing Interests: SLG has received a research
grant, travel reimbursements and honoraria from Novartis. SLG has also consulted
for, received travel reimbursements and honoraria from Janssen, Eli Lilly, Amgen
and Pfizer. There are no other conflicts of interest. This does not alter the
authors' adherence to PLOS ONE policies on sharing data and materials.


87. Br Dent J. 2014 Jun;216(12):657. doi: 10.1038/sj.bdj.2014.507.

Gum disease reversed in LAD patients.

Pacey L.

DOI: 10.1038/sj.bdj.2014.507
PMID: 24970504 [Indexed for MEDLINE]


88. Clin Lab. 2016;62(5):963-5. doi: 10.7754/clin.lab.2015.150933.

IL-17 ELISpot as Predictor for Kidney Allograft Rejection?

Lindemann M, Könemann J, Horn PA, Witzke O.

BACKGROUND: IL-17 expression in kidney biopsies had been described as predictive
of allograft rejection.
METHODS: We tested the hypothesis that IL-17A ELISpot responses towards a pool
of third party cells could predict acute rejections of kidney allografts. This
assay determines alloresponses but does not require donor cells. IL-17A ELISpot
assays were performed in 50 kidney transplant recipients prior to
transplantation. Seventeen of the recipients suffered from acute allograft
rejection.
RESULTS: We observed that the amount of IL-17A producing T cells did not differ
between transplant recipients with and without kidney allograft rejection,
rebutting our hypothesis. Further, we found that the alloreactivity before
transplantation correlated with the reaction against the mitogen
phythohemagglutinin (r = 0.5, p = 0.0009).
CONCLUSIONS: IL-17A ELISpot was not predictive of acute kidney allografts
rejection. But ELISpots after stimulation with allogeneic cells and
phythohemagglutinin could similarly detect the "general" capacity of T cells to
secrete IL-17A.

DOI: 10.7754/clin.lab.2015.150933
PMID: 27349025 [Indexed for MEDLINE]


89. Genet Mol Res. 2015 Jul 13;14(3):7721-6. doi: 10.4238/2015.July.13.18.

Stimulation of bacterial biofilms on Th17 immune cells.

Wang GQ(1), Wang L(2), Zhang HL(2), Dong YQ(2), Yang YX(3).

Author information:
(1)Clinical Laboratory of the First Affiliated Hospital, XinXiang Medical
University, Henan Weihui, China wgqiang345@163.com.
(2)Clinical Laboratory of the First Affiliated Hospital, XinXiang Medical
University, Henan Weihui, China.
(3)Department of Ophthalmology, The First Affiliated Hospital, Xinxiang Medical
University, Henan Weihui, China.

We investigated the role of bacterial biofilms in stimulating T helper 17 (Th17)
cells in infected organisms. The formation of bacterial biofilms isolated from
clinical lavage fluid samples was measured. Th17 cells and interleukin 17
(IL-17) levels in the peripheral blood of healthy individuals, people infected
by biofilm bacteria, people infected by non-biofilm bacteria, and in the lavage
fluid from people infected by bacteria were determined. Differences in those
data were tested using the SPSS 17.0 statistical software. Th17 cells and IL-17
levels in the peripheral blood of biofilm bacteria-infected people, non-biofilm
bacteria-infected people, and healthy controls were 0.59 ± 0.18% and 108.8 ±
20.5 pg/mL; 0.58 ± 0.18% and 100.1 ± 20.7 pg/mL; and 0.55 ± 0.17% and 100.0 ±
21.4 pg/mL, respectively; there were no statistically significant differences (P
> 0.05). Th17 cells and IL-17 levels in the lavage fluid of biofilm
bacteria-infected people and non-biofilm bacteria-infected people were 1.37 ±
0.34% and 157.4 ± 30.8 pg/mL; and 1.11 ± 0.21% and 136.2 ± 24.3 mg/mL,
respectively; the differences were statistically significant (P < 0.05).
Bacterial biofilms can increase the expression levels of Th17 cells and IL-17 in
local infections; this may be the mechanism by which chronic injuries are caused
by biofilm infections.

DOI: 10.4238/2015.July.13.18
PMID: 26214453 [Indexed for MEDLINE]


90. Hypertension. 2014 Aug;64(2):224-6. doi: 10.1161/HYPERTENSIONAHA.114.03340.

In search of the T cell involved in hypertension and target organ damage.

Guzik TJ, Mikolajczyk T.

Comment on
    Hypertension. 2014 Aug;64(2):305-14.

DOI: 10.1161/HYPERTENSIONAHA.114.03340
PMID: 24866136 [Indexed for MEDLINE]


91. Zhonghua Fu Chan Ke Za Zhi. 2005 Jun;40(6):380-2.

[Determination of interleukin-17 concentrations in peritoneal fluid of women
with endometriosis].

[Article in Chinese]

Zhang XM(1), Lin J, Xu H, Deng L, Qian YL.

Author information:
(1)Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang
University, Hangzhou 310006, China.

OBJECTIVE: To investigate the role of interleukin-17 (IL-17) in the pathogenesis
of endometriosis.
METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect the
concentrations of IL-17 in peritoneal fluid of 36 patients with different stage
endometriosis and 26 patients without endometriosis.
RESULTS: The concentrations of IL-17 in peritoneal fluid of the patients with
and without endometriosis were (5.7 +/- 1.9) ng/L and (5.3 +/- 1.4) ng/L,
respectively, without significant difference between the two groups (P > 0.05).
According to staging criteria of r-AFS, the concentrations of peritoneal IL-17
in the patients with stage I-II endometriosis (6.4 +/- 1.7) ng/L were
significantly higher than those in the patients with stage III-IV endometriosis
(5.1 +/- 1.8) ng/L and in the patients without endometriosis (P < 0.05). There
was no difference with regard to peritoneal IL-17 concentrations between
proliferative and secretory phases in the patients with or without endometriosis
(P > 0.05). The levels of peritoneal IL-17 were significantly higher in the
endometriosis patients with infertility (6.4 +/- 1.8) ng/L than in the
endometriosis patients without infertility (5.1 +/- 1.8) ng/L (P < 0.05).
CONCLUSION: IL-17 may play an important role in the pathogenesis of early
endometriosis and pathophysiology of endometriosis-associated infertility.

PMID: 16008887 [Indexed for MEDLINE]


92. BMC Infect Dis. 2014 Feb 1;14:55. doi: 10.1186/1471-2334-14-55.

IFN- alpha blocks IL-17 production by peripheral blood mononuclear cells in
patients with chronic active hepatitis B Infection.

Cui F(1), Meng J, Luo P, Chen P.

Author information:
(1)Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing
Medical University, No, 1 Youyi Road, Chongqing, Yuzhong District, China.
cuihpp@126.com.

BACKGROUND: IFN-α has been used to treat patients with chronic active hepatitis
B (CAHB). Recent studies have implicated the IL-23/Th-17 pathway in the
pathogenesis of CAHB. In this study, we investigated whether IFN-α could affect
this pathway.
METHODS: Peripheral blood mononuclear cells (PBMCs) obtained from patients with
active CAHB (n = 61) and controls (n = 32) were cultured with or without IFN-α,
and the levels of IL-17 and IL-10 in the supernatants were determined by ELISA,
while the frequency of IL-17-expressing cells was measured by FACS. Similar
experiments were also conducted with isolated CD4+ T cells from controls.
Furthermore, an experiment using an anti-IL-10 antibody was performed to examine
the underlying mechanisms of action of IFN-α.
RESULTS: Both the levels of IL-17 and the frequency of IL-17-expressing cells
were significantly higher in the PBMCs from CAHB patients than in the controls.
IFN-α significantly decreased IL-17 production and the frequency of
IL-17-expressing cells in PBMCs from both patients and controls. On the other
hand, IFN-α increased IL-10 production by PBMCs from patients and controls.
Anti-IL-10 antibody was able to neutralize the inhibitory effect of IFN-α on
IL-17 production by PBMCs.
CONCLUSIONS: In vitro experiments showed that IFN-α could inhibit IL-17
expression and increase IL-10 production by PBMCs and CD4+ T cells. The
inhibitory role of IFN-α on IL-17 production was partly mediated by IL-10.

DOI: 10.1186/1471-2334-14-55
PMCID: PMC3922633
PMID: 24484458 [Indexed for MEDLINE]


93. Oncotarget. 2017 Mar 21;8(12):18914-18923. doi: 10.18632/oncotarget.14835.

IL-17B activated mesenchymal stem cells enhance proliferation and migration of
gastric cancer cells.

Bie Q(1), Zhang B(1), Sun C(2), Ji X(1), Barnie PA(3), Qi C(1), Peng J(1), Zhang
D(1), Zheng D(1), Su Z(1), Wang S(1)(4), Xu H(1)(4).

Author information:
(1)Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang,
Jiangsu, China.
(2)Department of Anesthesiology, The Affiliated Hospital of Jiangsu University,
Zhenjiang, Jiangsu, China.
(3)Department of Biomedical and Forensic Sciences, School of Biological
Sciences, University of Cape Coast, Cape Coast, Ghana.
(4)Key Laboratory of Laboratory Medicine of Jiangsu Province, School of
Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Mesenchymal stem cells are important cells in tumor microenvironment. We have
previously demonstrated that IL-17B/IL-17RB signal promoted progression of
gastric cancer. In this study, we further explored the effect of IL-17B on
mesenchymal stem cells in tumor microenvironment and its impact on the tumor
progression. The results showed that IL-17B induced the expression of
stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and
enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal
stem cells after treating with exogenous rIL-17B promoted the proliferation and
migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal
stem cells to produce soluble factors. In addition, rIL-17B also activated the
NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a
new mechanism that IL-17B enhanced the progression of gastric cancer by
activating mesenchymal stem cells.

DOI: 10.18632/oncotarget.14835
PMCID: PMC5386657
PMID: 28145881 [Indexed for MEDLINE]

Conflict of interest statement: CONFLICTS OF INTEREST The authors have no
financial conflicts of interest.


94. Indian Pediatr. 2015 Jun;52(6):473-4. doi: 10.1007/s13312-015-0658-2.

Biomarkers for Diagnosis of Kawasaki Disease.

Rawat A(1), Singh S.

Author information:
(1)Pediatric Allergy Immunology Unit, Advanced Pediatrics Center, PGIMER,
Chandigarh, India. surjitsinghpgi@rediffmail.com.

Comment on
    Indian Pediatr. 2015 Jun;52(6):477-80.

DOI: 10.1007/s13312-015-0658-2
PMID: 26121719 [Indexed for MEDLINE]


95. J Allergy Clin Immunol. 2014 May;133(5):1495-6, 1496.e1. doi:
10.1016/j.jaci.2013.12.1095. Epub 2014 Mar 15.

DEP-induced T(H)17 response in asthmatic subjects.

Inoue K(1), Tanaka M(2), Takano H(3).

Author information:
(1)Center for Medical Science, International University of Health and Welfare,
Ohtawara, Japan. Electronic address: kinoue@iuhw.ac.jp.
(2)Center for Medical Science, International University of Health and Welfare,
Ohtawara, Japan.
(3)Graduate School of Engineering, Kyoto University, Kyoto, Japan.

Comment in
    J Allergy Clin Immunol. 2014 May;133(5):1496-7.

Comment on
    J Allergy Clin Immunol. 2013 Nov;132(5):1194-1204.e2.

DOI: 10.1016/j.jaci.2013.12.1095
PMID: 24636096 [Indexed for MEDLINE]


96. Korean J Ophthalmol. 2011 Apr;25(2):73-6. doi: 10.3341/kjo.2011.25.2.73. Epub
2011 Mar 11.

Investigating the relationship between serum interleukin-17 levels and systemic
immune-mediated disease in patients with dry eye syndrome.

Oh JY(1), Kim MK, Choi HJ, Ko JH, Kang EJ, Lee HJ, Wee WR, Lee JH.

Author information:
(1)Seoul Artificial Eye Center, Seoul National University Hospital Clinical
Research Institute, Seoul, Korea.

PURPOSE: To investigate the association between dry eye syndrome (DE) and serum
levels of interleukin (IL)-17 in patients with systemic immune-mediated
diseases.
METHODS: IL-17 and IL-23 levels were measured in the sera of patients whose tear
production was <5 mm on the Schirmer test. Subjects included patients with
chronic graft-versus-host disease (GVHD), rheumatoid arthritis (RA), Sjogren's
syndrome (SS), systemic lupus erythematosus (SLE), and no systemic disease.
Corneal/conjunctival fluorescein staining was scored and the correlation between
the score and the IL-17 level was evaluated.
RESULTS: A strong correlation existed between IL-17 level and the type of
systemic disease. IL-17 was significantly elevated in patients with chronic GVHD
compared to those with RA and SS. IL-17 was not detectable in patients with SLE
or in those without systemic disease. IL-23 was not detected in any of the
subjects. IL-17 was significantly increased in patients with high fluorescein
staining scores.
CONCLUSIONS: Our data suggest that IL-17 is involved in the pathogenesis of DE
in patients with systemic immune-mediated diseases.

© 2011 The Korean Ophthalmological Society

DOI: 10.3341/kjo.2011.25.2.73
PMCID: PMC3060396
PMID: 21461217 [Indexed for MEDLINE]

Conflict of interest statement: No potential conflict of interest relevant to
this article was reported.


97. J Invest Dermatol. 2015 Apr;135(4):1025-1032. doi: 10.1038/jid.2014.532. Epub
2014 Dec 19.

IL-36γ (IL-1F9) is a biomarker for psoriasis skin lesions.

D'Erme AM(1), Wilsmann-Theis D(2), Wagenpfeil J(2), Hölzel M(3), Ferring-Schmitt
S(2), Sternberg S(2), Wittmann M(4), Peters B(5), Bosio A(6), Bieber T(2),
Wenzel J(7).

Author information:
(1)Department of Dermatology, University of Bonn, Bonn, Germany; Division of
Dermatology, Department of Surgery and Translational Medicine, University of
Florence, Florence, Italy.
(2)Department of Dermatology, University of Bonn, Bonn, Germany.
(3)Institute of Clinical Chemistry and Clinical Pharmacology, University of
Bonn, Bonn, Germany.
(4)Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of
Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK; Centre
for Skin Sciences, University of Bradford, Bradford, UK.
(5)Deutsches Zentrum für Luft- und Raumfahrt, Project Management Health
Research, Bonn, Germany.
(6)Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
(7)Department of Dermatology, University of Bonn, Bonn, Germany. Electronic
address: joerg.wenzel@ukb.uni-bonn.de.

Comment in
    J Invest Dermatol. 2016 Jul;136(7):1520-1523.

In recent years, different genes and proteins have been highlighted as potential
biomarkers for psoriasis, one of the most common inflammatory skin diseases
worldwide. However, most of these markers are not only psoriasis-specific but
also found in other inflammatory disorders. We performed an unsupervised cluster
analysis of gene expression profiles in 150 psoriasis patients and other
inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema,
and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α
(TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ
was the most outstanding marker. In subsequent immunohistological analyses,
IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ
peripheral blood serum levels were found to be closely associated with disease
activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ
immunohistochemistry was found to be a helpful marker in the histological
differential diagnosis between psoriasis and eczema in diagnostically
challenging cases. These features highlight IL-36γ as a valuable biomarker in
psoriasis patients, both for diagnostic purposes and measurement of disease
activity during the clinical course. Furthermore, IL-36γ might also provide a
future drug target, because of its potential amplifier role in TNFα- and IL-17
pathways in psoriatic skin inflammation.

DOI: 10.1038/jid.2014.532
PMID: 25525775 [Indexed for MEDLINE]


98. FASEB J. 2016 Feb;30(2):874-83. doi: 10.1096/fj.15-274845. Epub 2015 Nov 2.

Extracellular adenosine levels are associated with the progression and
exacerbation of pulmonary fibrosis.

Luo F(1), Le NB(1), Mills T(1), Chen NY(1), Karmouty-Quintana H(1), Molina
JG(1), Davies J(1), Philip K(1), Volcik KA(1), Liu H(1), Xia Y(1), Eltzschig
HK(1), Blackburn MR(2).

Author information:
(1)*Department of Biochemistry and Molecular Biology, University of Texas
Medical School at Houston, Houston, Texas, USA; Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas,
USA; and Department of Anesthesiology, University of Colorado Denver, Aurora,
Colorado, USA.
(2)*Department of Biochemistry and Molecular Biology, University of Texas
Medical School at Houston, Houston, Texas, USA; Division of Neonatal-Perinatal
Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas,
USA; and Department of Anesthesiology, University of Colorado Denver, Aurora,
Colorado, USA michael.r.blackburn@uth.tmc.edu.

Idiopathic pulmonary fibrosis is a devastating lung disease with limited
treatment options. The signaling molecule adenosine is produced in response to
injury and serves a protective role in early stages of injury and is detrimental
during chronic stages of disease such as seen in lung conditions such as
pulmonary fibrosis. Understanding the association of extracellular adenosine
levels and the progression of pulmonary fibrosis is critical for designing
adenosine based approaches to treat pulmonary fibrosis. The goal of this study
was to use various models of experimental lung fibrosis to understand when
adenosine levels are elevated during pulmonary fibrosis and whether these
elevations were associated with disease progression and severity. To accomplish
this, extracellular adenosine levels, defined as adenosine levels found in
bronchioalveolar lavage fluid, were determined in mouse models of resolvable and
progressive pulmonary fibrosis. We found that relative bronchioalveolar lavage
fluid adenosine levels are progressively elevated in association with pulmonary
fibrosis and that adenosine levels diminish in association with the resolution
of lung fibrosis. In addition, treatment of these models with dipyridamole, an
inhibitor of nucleoside transporters that potentiates extracellular adenosine
levels, demonstrated that the resolution of lung fibrosis is blocked by the
failure of adenosine levels to subside. Furthermore, exacerbating adenosine
levels led to worse fibrosis in a progressive fibrosis model. Increased
adenosine levels were associated with elevation of IL-6 and IL-17, which are
important inflammatory cytokines in pulmonary fibrosis. These results
demonstrate that extracellular adenosine levels are closely associated with the
progression of experimental pulmonary fibrosis and that this signaling pathway
may mediate fibrosis by regulating IL-6 and IL-17 production.

© FASEB.

DOI: 10.1096/fj.15-274845
PMCID: PMC4714555
PMID: 26527068 [Indexed for MEDLINE]


99. Oncotarget. 2017 Apr 25;8(17):29370-29382. doi: 10.18632/oncotarget.14083.

Changes of circulating Th22 cells in children with hand, foot, and mouth disease
caused by enterovirus 71 infection.

Cui D(1)(2), Zhong F(3), Lin J(4), Wu Y(5), Long Q(1)(2), Yang X(1)(2), Zhu
Q(1)(2), Huang L(1)(2), Mao Q(1)(2), Huo Z(1)(2), Zhou Z(1)(2), Xie G(1)(2),
Zheng S(1)(2), Yu F(1)(2), Chen Y(1)(2).

Author information:
(1)Department of Laboratory Medicine, First Affiliated Hospital, College of
Medicine, Zhejiang University, Hangzhou, China.
(2)Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang
Province, Hangzhou, China.
(3)Department of General Surgery, the Second Affiliated Hospital of Soochow
University, Suzhou, China.
(4)Department of Clinical Laboratory, Center of Community Health Service of
Qingbo Street, Hangzhou, China.
(5)Clinical Laboratory, Hangzhou Children's Hospital, Hangzhou, China.

Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of
autoimmune diseases and infectious diseases, although the role of Th22 cells
remains largely unclear in children with hand, foot, and mouth disease (HFMD)
caused by enterovirus 71 (EV71). This study aims to explore the role of
circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated
HFMD. We found that during the acute stage of illness, the frequencies of cTh22
and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom
affected patients, and especially in severely affected patients, were
significantly higher than in healthy controls (HC). The major source of IL-22
production was cTh22 cells, partially from cTh17 cells. Moreover, the protein
and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly
different among the mild patients, severe patients and HC, as well as AHR and
RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels
and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies.
Furthermore, the frequencies of cTh22 were significantly decreased in the
convalescent patients. Our findings indicated that cTh22 cells could play
critical roles in the pathogenesis of EV71 infection, and are potential
therapeutic targets for patients with EV71-associated HFMD.

DOI: 10.18632/oncotarget.14083
PMCID: PMC5438737
PMID: 28030850 [Indexed for MEDLINE]

Conflict of interest statement: CONFLICTS OF INTEREST The authors have declared
that no competing interests exist.


100. Cytokine. 2014 Feb;65(2):167-74. doi: 10.1016/j.cyto.2013.11.007. Epub 2013 Dec
15.

The role of interchain disulfide bond in a recombinant human interleukin-17A
variant.

Wu B(1), Muzammil S(2), Jones B(3), Nemeth JF(2), Janecki DJ(2), Baker A(2),
Merle Elloso M(3), Naso M(2), Carton J(2), Taudte S(2).

Author information:
(1)Biologics Research, Janssen Research and Development, LLC., 1400 McKean Road,
Spring House, PA 19477, United States. Electronic address: bwu63@its.jnj.com.
(2)Biologics Research, Janssen Research and Development, LLC., 1400 McKean Road,
Spring House, PA 19477, United States.
(3)Immunology Discovery Research, Janssen Research and Development, LLC., 1400
McKean Road, Spring House, PA 19477, United States.

Interleukin-17A (IL-17A) is the prototype of IL-17 family and has been
implicated in the pathogenesis of a variety of autoimmune diseases. Therefore
its structural and functional properties are of great medical interest. During
our research on a recombinant human IL-17A (rhIL-17A) variant, four isoforms
were obtained when it was refolded. While isoforms 1 and 2 represented
non-covalent dimers, isoforms 3 and 4 were determined to be covalent dimers. All
four isoforms were structurally similar by Circular Dichroism and fluorescence
spectroscopy studies, but differential scanning calorimetry demonstrated thermal
stability in the order of isoform 1=isoform 2<isoform 4<isoform 3. In addition,
compared to covalent dimers (isoform 3 and 4), the non-covalent dimers (isoforms
1 and 2) are slightly less active in a receptor-binding assay but at least
5-fold less active in a cell-based assay.

Copyright © 2013 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.cyto.2013.11.007
PMID: 24345576 [Indexed for MEDLINE]


101. Mediators Inflamm. 2016;2016:3296307. doi: 10.1155/2016/3296307. Epub 2016 Feb
25.

Correlation of Surface Toll-Like Receptor 9 Expression with IL-17 Production in
Neutrophils during Septic Peritonitis in Mice Induced by E. coli.

Ren Y(1), Hua L(2), Meng X(3), Xiao Y(4), Hao X(2), Guo S(4), Zhao P(2), Wang
L(4), Dong B(2), Yu Y(2), Wang L(4).

Author information:
(1)Department of Molecular Biology in College of Basic Medical Sciences and
Institute of Pediatrics in First Hospital, Jilin University, Changchun 130021,
China; Department of Endodontics, School and Hospital of Stomatology, Jilin
University, Changchun 130021, China.
(2)Department of Immunology in College of Basic Medical Sciences, Jilin
University, Changchun 130021, China.
(3)Department of Endodontics, School and Hospital of Stomatology, Jilin
University, Changchun 130021, China; Department of Immunology in College of
Basic Medical Sciences, Jilin University, Changchun 130021, China.
(4)Department of Molecular Biology in College of Basic Medical Sciences and
Institute of Pediatrics in First Hospital, Jilin University, Changchun 130021,
China.

IL-17 is a proinflammatory cytokine produced by various immune cells.
Polymorphonuclear neutrophils (PMNs) are the first line of defense in bacterial
infection and express surface Toll-like receptor 9 (sTLR9). To study the
relationship of sTLR9 and IL-17 in PMNs during bacterial infection, we infected
mice with E. coli intraperitoneally to establish a septic peritonitis model for
studying the PMNs response in peritoneal cavity. We found that PMNs and some of
"giant cells" were massively accumulated in the peritoneal cavity of mice with
fatal septic peritonitis induced by E. coli. Kinetically, the CD11b(+) PMNs were
increased from 20-40% at 18 hours to >80% at 72 hours after infection. After E.
coli infection, sTLR9 expression on CD11b(+) and CD11b(-) PMNs and macrophages
in the PLCs were increased at early stage and deceased at late stage; IL-17
expression was also increased in CD11b(+) PMNs, CD11b(-) PMNs, macrophages, and
CD3(+) T cells. Using experiments of in vitro blockage, qRT-PCR and cell
sorting, we confirmed that PMNs in the PLCs did increase their IL-17 expression
during E. coli infection. Interestingly, sTLR9(-)CD11b(+)Ly6G(+) PMNs, not
sTLR9(+)CD11b(+)Ly6G(+) PMNs, were found to be able to increase their IL-17
expression. Together, the data may help understand novel roles of PMNs in septic
peritonitis.

DOI: 10.1155/2016/3296307
PMCID: PMC4785266
PMID: 27057095 [Indexed for MEDLINE]


102. Immunity. 2014 Jan 16;40(1):10-2. doi: 10.1016/j.immuni.2013.12.006.

Th17 cells at the crossroads of autoimmunity, inflammation, and atherosclerosis.

van Bruggen N(1), Ouyang W(2).

Author information:
(1)Department of Biomedical Imaging, Genentech Inc., South San Francisco, CA
94080, USA. Electronic address: vbruggen@gene.com.
(2)Department of Immunology, Genentech Inc., South San Francisco, CA 94080, USA.
Electronic address: ouyang@gene.com.

Comment on
    Immunity. 2014 Jan 16;40(1):153-65.

The connection between inflammation, autoimmunity, and atherosclerosis is long
established. In this issue of Immunity, Lim et al. (2014) demonstrate that
oxidized low-density lipoprotein is one of the key environmental factors driving
the development of inflammatory T helper 17 cells in atherosclerosis.

Copyright © 2014 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.immuni.2013.12.006
PMID: 24439264 [Indexed for MEDLINE]


103. Arthritis Rheum. 2011 Aug;63(8):2168-71. doi: 10.1002/art.30331.

Interleukin-17 and Th17 cells: from adult to juvenile arthritis--now it is
serious!

Miossec P.

Comment on
    Arthritis Rheum. 2011 Aug;63(8):2504-15.

DOI: 10.1002/art.30331
PMID: 21380999 [Indexed for MEDLINE]


104. Neuro Endocrinol Lett. 2010;31(6):852-6.

Growth hormone-releasing hormone stimulates the secretion of interleukin 17 from
human peripheral blood mononuclear cells in vitro.

Stepien T(1), Lawnicka H, Komorowski J, Stepien H, Siejka A.

Author information:
(1)Department of General and Endocrinological Surgery, Copernicus Memorial
Hospital, Pabianicka Street 62, 93-513 Lodz, Poland.

OBJECTIVES: Growth hormone-releasing hormone (GHRH) plays a crucial role in the
secretion of GH from the pituitary, acts as a growth factor in variety of cancer
cells and possesses immunomodulatory activity. Interleukin(IL)-17 apart from its
pro-inflammatory role has been also shown to play a role in carcinogenesis. The
effect of GHRH on the IL-17 has not been studied so far.
AIM: To evaluate the effect of GHRH on the secretion of IL-17 from human
peripheral blood mononuclear cells (PBMC) in vitro.
MATERIALS AND METHODS: The concentrations of IL-17 in supernatants from PBMC
cultured for 24 hrs were assessed using ELISA kit.
RESULTS: We show for the first time that GHRH can stimulate the secretion of
IL-17 from human PBMC in 24 hrs culture, and that GHRH antagonist counteracts
this effect.
CONCLUSION: Our study further elucidates the immunomodulatory role of GHRH.

PMID: 21196925 [Indexed for MEDLINE]


105. Anticancer Res. 2006 Nov-Dec;26(6B):4213-6.

Expression of interleukin-17 in human colorectal cancer.

Wägsäter D(1), Löfgren S, Hugander A, Dimberg J.

Author information:
(1)Atherosclerosis Research Unit, King Gustav V Research Institute, Department
of Medicine, Karolinska Institute, SE-171 76 Stockholm.

The proinflammatory cytokine IL-17 plays a potential role in T-cell mediated
angiogenesis and promotes tumourigenicity of human cervical cancer. The
objective of this study was to determine whether IL-17 protein level is altered
in colorectal tumours (n=74) compared with paired normal mucosa and in plasma
from patients (n=61) with colorectal cancer (CRC) compared with a healthy group
(n=78). Analyses by ELISA showed that IL-17 protein was undetectable in 48.6% of
the patients with cancer, as well as corresponding normal tissue which may in
part reflect an individual difference. No significant difference was observed
regarding IL-17 protein levels between cancer and matched normal tissue or in
plasma between patients and the healthy group. Immunohistochemistry (n=20)
revealed heterogenous immunoreactivity in 65% of the cases. The results of this
study suggest that IL-17 plays a minor or partial role in CRC.

PMID: 17201135 [Indexed for MEDLINE]


106. Med Hypotheses. 2014 Sep;83(3):404-6. doi: 10.1016/j.mehy.2014.07.006. Epub 2014
Jul 18.

Melatonin as potential inducer of Th17 cell differentiation.

Kuklina EM(1).

Author information:
(1)Laboratory of Immunoregulation, Institute of Ecology and Genetics of
Microorganisms, Russian Academy of Sciences, Goleva Str. 13, Perm, Russian
Federation. Electronic address: ibis_07@mail.ru.

The subset of T lymphocytes producing IL-17 (Th17) plays a key role in the
immune system. It has been implicated in host defense, inflammatory diseases,
tumorigenesis, autoimmune diseases, and transplant rejection. Careful analysis
of the data available holds that Th17 cell subpopulation should be under the
direct control of pineal hormone melatonin: the key Th17 differentiation factor
RORα serves in the meantime as a high-affinity melatonin receptor. Since the
levels of melatonin have diurnal and seasonal variation, as well as substantial
deviations in some physiological or pathological conditions, melatonin-dependent
regulation of Th17 cells should implicate multiform manifestation, such as
influencing the outcome of infectious challenge or determining predisposition,
etiology and progression of immune-related morbidities. Another important reason
to raise a point of the new melatonin effects is current considering the
possibilities of its clinical trials. Especially, the differentiation of Th17
upon melatonin treatment must aggravate the current recession in autoimmune
diseases or induce serious complications in pregnancy.

Copyright © 2014 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.mehy.2014.07.006
PMID: 25064379 [Indexed for MEDLINE]


107. Eur J Immunol. 2012 Sep;42(9):2246-54. doi: 10.1002/eji.201242605.

Immunity to infection in IL-17-deficient mice and humans.

Cypowyj S(1), Picard C, Maródi L, Casanova JL, Puel A.

Author information:
(1)St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller
Branch, The Rockefeller University, New York, NY, USA. socy641@rockefeller.edu

Mice with defective IL-17 immunity display a broad vulnerability to various
infectious agents at diverse mucocutaneous surfaces. In humans, the study of
patients with various primary immunodeficiencies, including autosomal dominant
hyper-IgE syndrome caused by dominant-negative STAT3 mutations and autosomal
recessive autoimmune polyendocrinopathy syndrome type 1 caused by null mutations
in AIRE, has suggested that IL-17A, IL-17F and/or IL-22 are essential for
mucocutaneous immunity to Candida albicans. This hypothesis was confirmed by the
identification of rare patients with chronic mucocutaneous candidiasis (CMC) due
to autosomal recessive IL-17RA deficiency and autosomal dominant IL-17F
deficiency. Heterozygosity for gain-of-function mutations in STAT1 in additional
patients with CMC was recently shown to inhibit the development of IL-17 T
cells. Although the infectious phenotype of patients with CMC and inborn errors
of IL-17 immunity remains to be finely delineated, it appears that human IL-17A
and IL-17F display redundancy for protective immunity in natural conditions that
is not seen in their mouse orthologs in experimental conditions.

© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI: 10.1002/eji.201242605
PMCID: PMC3720135
PMID: 22949323 [Indexed for MEDLINE]


108. Immun Inflamm Dis. 2016 Aug 24;4(4):401-412. doi: 10.1002/iid3.121. eCollection
2016 Dec.

Involvement of IL-17A-producing TCR γδ T cells in late protective immunity
against pulmonary Mycobacterium tuberculosis infection.

Umemura M(1), Okamoto-Yoshida Y(2), Yahagi A(2), Touyama S(1), Nakae S(3),
Iwakura Y(4), Matsuzaki G(1).

Author information:
(1)Molecular Microbiology GroupDepartment of Infectious DiseasesTropical
Biosphere Research CenterUniversity of the Ryukyus1
SenbaruNishiharaOkinawa903-0213Japan; Department of Host DefenseGraduate School
of MedicineUniversity of the Ryukyus1 SenbaruNishiharaOkinawa903-0213Japan.
(2)Molecular Microbiology Group Department of Infectious Diseases Tropical
Biosphere Research Center University of the Ryukyus 1 Senbaru Nishihara Okinawa
903-0213 Japan.
(3)Laboratory of Systems Biology Center for Experimental Medicine and Systems
Biology Institute of Medical Science University of Tokyo 4-6-1 Shiroganedai
Minato-ku Tokyo 108-8639 Japan.
(4)Division of Experimental Animal Immunology Center for Animal Disease Models
Research Institute for Biomedical Sciences Tokyo University of Science Chiba
278-0022 Japan.

INTRODUCTION: Interleukin (IL)-17A is a cytokine originally reported to induce
neutrophil-mediated inflammation and anti-microbial activity. The CD4+ T cells,
which produce IL-17A, have been well characterized as Th17 cells. On the other
hand, IL-17A-producing TCR γδ+ T cells have been reported to participate in the
immune response at an early stage of infection with Listeria monocytogenes and
Mycobacterium bovis in mice. However, the involvement of IL-17A in protective
immunity was not clearly demonstrated in the chronic stage of M.
tuberculosis-infected mice.
METHODS: We analyzed role of IL-17A in host defense against chronically infected
M. tuberculosis using IL-17A KO mice.
RESULTS: We found that TCR γδ+ T cells are a primary source of IL-17A, but that
mycobacterial antigen-specific Th17 cells were hardly detected even at the
chronic stage of M. tuberculosis infection. IL-17A-deficient mice showed a
decreased survival rate, and increased bacterial burden in the lungs after the
infection when compared to the wild-type mice. Furthermore, a histological
analysis showed an impaired granuloma formation in the infected lungs of
IL-17A-deficient mice, which was considered to be due to a decrease of IFN-γ and
TNF at the chronic stage.
CONCLUSION: Our data suggest that the IL-17A-producing TCR γδ+ T cells, rather
than the Th17 cells, in the infected lungs are an indispensable source of
protective immunity against M. tuberculosis infection.

DOI: 10.1002/iid3.121
PMCID: PMC5134718
PMID: 27980775 [Indexed for MEDLINE]


109. Molecules. 2015 May 15;20(5):8816-22. doi: 10.3390/molecules20058816.

Almond Skin Inhibits HSV-2 Replication in Peripheral Blood Mononuclear Cells by
Modulating the Cytokine Network.

Arena A(1), Bisignano C(2), Stassi G(3), Filocamo A(4), Mandalari G(4).

Author information:
(1)Department of Human Pathology, Policlinico Universitario, Via C. Valeria,
Messina 98125, Italy. aarena@unime.it.
(2)Department of Biological and Environmental Science, University of Messina,
Sal. Sperone 31, Messina 98100, Italy. cbisignano@unime.it.
(3)Department of Human Pathology, Policlinico Universitario, Via C. Valeria,
Messina 98125, Italy. gstassi@unime.it.
(4)Department of Drug Science and Products for Health, Vill. SS. Annunziata,
Messina 98100, Italy. afilocamo@unime.it.

We have investigated the effect of almond skin extracts on the production of
pro-inflammatory and anti-inflammatory cytokines in human peripheral blood
mononuclear cells (PBMCs). PBMCs were either infected or not by herpes simplex
virus type 2 (HSV-2), with and without prior treatment with almond skin
extracts. Production of IL-17 induced by HSV-2 was inhibited by natural skins
(NS) treatment. NS triggered PBMC in releasing IFN-α, IFN-γ and IL-4 in cellular
supernatants. These results may explain the antiviral potential of almond skins.

DOI: 10.3390/molecules20058816
PMCID: PMC6272138
PMID: 25988612 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflict of interest.