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

Hideki Ogura, Masaaki Murakami, Yuko Okuyama, Mineko Tsuruoka, Chika Kitabayashi, Minoru Kanamoto, Mika Nishihara, Yoichiro Iwakura, Toshio Hirano

Research output: Contribution to journalArticle

328 Citations (Scopus)

Abstract

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-feedback loop of IL-6 signaling, which involved the activation of the transcription factors nuclear factor (NF)-κB 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.

Original languageEnglish
Pages (from-to)628-636
Number of pages9
JournalImmunity
Volume29
Issue number4
DOIs
Publication statusPublished - 2008 Oct 17
Externally publishedYes

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Ogura, H., Murakami, M., Okuyama, Y., Tsuruoka, M., Kitabayashi, C., Kanamoto, M., Nishihara, M., Iwakura, Y., & Hirano, T. (2008). Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction. Immunity, 29(4), 628-636. https://doi.org/10.1016/j.immuni.2008.07.018