The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by antagonizing signaling via the receptor for IL-6

作者：Nagashima Hiroyuki; Okuyama Yuko; Asao Atsuko; Kawabe Takeshi; Yamaki Satoshi; Nakano Hiroyasu; Croft Michael; Ishii Naoto; So Takanori^*

来源：Nature Immunology, 2014, 15(5): 449-+.

DOI：10.1038/ni.2863

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 T(H)17 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.

• 出版日期2014-5