Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction

被引：658

作者：

Ogura, Hideki ^{[4
,5
,6
]}

Murakami, Masaaki ^{[4
,5
,6
]}

Okuyama, Yuko ^{[4
,5
,6
]}

Tsuruoka, Mineko ^{[4
,5
,6
]}

Kitabayashi, Chika ^{[4
,5
,6
]}

Kanamoto, Minoru ^{[4
,5
,6
]}

Nishihara, Mika ^{[4
,5
,6
]}

Iwakura, Yoichiro ^{[2
,3
]}

Hirano, Toshio ^{[1
,4
,5
,6
]}

机构：

[1] RIKEN, Res Ctr Allergy & Immunol, Lab Cytokine Signaling, Yokohama, Kanagawa 2300045, Japan

[2] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo 1088639, Japan

[3] Univ Tokyo, Japan Sci & Technol Agcy, CREST Program, Tokyo 1088639, Japan

[4] Osaka Univ, Lab Dev Immunol, Osaka 5650871, Japan

[5] Osaka Univ, Japan Sci & Technol Agcy, CREST Program, Grad Sch Frontier Biosci,Grad Sch Med, Osaka 5650871, Japan

[6] Osaka Univ, WPI Immunol Frontier Res Ctr, Osaka 5650871, Japan

来源：

IMMUNITY | 2008年 / 29卷 / 04期

关键词：

D O I：

10.1016/j.immuni.2008.07.018

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

Dysregulated cytokine expression and signaling are major contributors to a number of autoimmune diseases. Interleukin-17A (IL-17A) and IL-6 are important in many disorders characterized by immune self-recognition, and IL-6 is known to induce the differentiation of T helper 17 (Th17) cells. Here we described an IL-17A-triggered positive-feed back loop of IL-6 signaling, which involved the activation of the transcription factors nuclear factor (NF)-kappa B and signal transducer and activator of transcription 3 (STAT3) in fibroblasts. Importantly, enhancement of this loop caused by disruption of suppressor of cytokine signaling 3 (SOCS3)-dependent negative regulation of the IL-6 signal transducer gp130 contributed to the development of arthritis. Because this mechanism also enhanced experimental autoimmune encephalomyelitis (EAE) in wild-type mice, it may be a general etiologic process underlying other Th17 cell-mediated autoimmune diseases.

引用

页码：628 / 636

页数：9

共 60 条

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The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease [J].