RRC ID 30710
Author Nagashima H, Okuyama Y, Asao A, Kawabe T, Yamaki S, Nakano H, Croft M, Ishii N, So T.
Title The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by antagonizing signaling via the receptor for IL-6.
Journal Nat Immunol
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.
Volume 15(5)
Pages 449-56
Published 2014-5-1
DOI 10.1038/ni.2863
PII ni.2863
Description HEK293T細胞に発現させ、IL6刺激によって引き起こされるSTAT3とIL6シグナル受容体gp130との結合、さらにTRAF5による阻害を調べるために使用されました。
PMID 24681564
PMC PMC4108451
MeSH Animals CD4 Antigens / metabolism Cell Differentiation / genetics Cells, Cultured Cytokine Receptor gp130 / metabolism* Disease Progression Encephalomyelitis, Autoimmune, Experimental / immunology* Interleukin-6 / immunology Mice Mice, Inbred Strains Mice, Knockout Myelin-Oligodendrocyte Glycoprotein / immunology Peptide Fragments / immunology STAT3 Transcription Factor / metabolism Signal Transduction / genetics T-Lymphocyte Subsets / immunology* TNF Receptor-Associated Factor 5 / genetics TNF Receptor-Associated Factor 5 / metabolism* Th17 Cells / immunology* Transcriptional Activation / genetics
IF 20.479
Times Cited 24
DNA material pEF-Flag-mSTAT3 (wild) (RDB02353).