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 language | English |
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Pages (from-to) | 628-636 |
Number of pages | 9 |
Journal | Immunity |
Volume | 29 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2008 Oct 17 |
Externally published | Yes |
Keywords
- CELLIMMUNO
- MOLIMMUNO
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases