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- Title
The adaptor TRAF5 limits the differentiation of inflammatory CD4<sup>+</sup> T cells by antagonizing signaling via the receptor for IL-6.
- Authors
Nagashima, Hiroyuki; Okuyama, Yuko; Asao, Atsuko; Kawabe, Takeshi; Yamaki, Satoshi; Nakano, Hiroyasu; Croft, Michael; Ishii, Naoto; So, Takanori
- Abstract
The physiological functions of members of the tumor-necrosis factor (TNF) receptor (TNFR)-associated factor (TRAF) family in T cell immunity are not well understood. We found that in the presence of interleukin 6 (IL-6), naive TRAF5-deficient CD4+ T cells showed an enhanced ability to differentiate into the TH17 subset of helper T cells. Accordingly, TH17 cell-associated experimental autoimmune encephalomyelitis (EAE) was greatly exaggerated in Traf5−/− mice. Although it is normally linked with TNFR signaling pathways, TRAF5 constitutively associated with a cytoplasmic region in the signal-transducing receptor gp130 that overlaps with the binding site for the transcription activator STAT3 and suppressed the recruitment and activation of STAT3 in response to IL-6. Our results identify TRAF5 as a negative regulator of the IL-6 receptor signaling pathway that limits the induction of proinflammatory CD4+ T cells that require IL-6 for their development.
- Subjects
T cell differentiation; ADAPTOR proteins; CD4 antigen; INTERLEUKIN-6; TUMOR necrosis factor receptors; T helper cells; STAT proteins
- Publication
Nature Immunology, 2014, Vol 15, Issue 5, p449
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2863