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Immunity. 2008 Oct 17;29(4):628-36. doi: 10.1016/j.immuni.2008.07.018. Epub 2008 Oct 9.

Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction.

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Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.


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)-kappaB 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.

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