Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction
| Autor: | Mineko Tsuruoka, Yoichiro Iwakura, Chika Kitabayashi, Hideki Ogura, Masaaki Murakami, Mika Nishihara, Toshio Hirano, Yuko Okuyama, Minoru Kanamoto |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
STAT3 Transcription Factor
Encephalomyelitis Autoimmune Experimental Immunology Autoimmunity Suppressor of Cytokine Signaling Proteins Mice medicine Cytokine Receptor gp130 Animals Immunology and Allergy SOCS3 STAT3 Interleukin 6 MOLIMMUNO Transcription factor Feedback Physiological biology Interleukin-6 Arthritis Experimental autoimmune encephalomyelitis Interleukin-17 NF-kappa B Fibroblasts medicine.disease Mice Mutant Strains Cell biology Mice Inbred C57BL Infectious Diseases CELLIMMUNO Suppressor of Cytokine Signaling 3 Protein STAT protein biology.protein Interleukin 17 Signal transduction Signal Transduction |
| Zdroj: | Immunity. 29(4):628-636 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2008.07.018 |
| Popis: | SummaryDysregulated 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. |
| Databáze: | OpenAIRE |
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