title: The adaptor TRAF5 limits the differentiation of inflammatory CD4(+) T cells by antagonizing signaling via the receptor for IL-6.
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.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagashima
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okuyama
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Asao
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawabe
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaki
authors.affiliation: 1] Department of Immunology, Juntendo University Graduate School of Medicine, Tokyo, Japan. [2] Department of Biochemistry, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
authors.affiliation: Division of Immune Regulation, La Jolla Institute, La Jolla, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: So
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130 / Q000378:metabolism*; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D048015:TNF Receptor-Associated Factor 5 / Q000235:genetics / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D015850:Interleukin-6; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D050796:STAT3 Transcription Factor; D048015:TNF Receptor-Associated Factor 5; C517781:myelin oligodendrocyte glycoprotein (34-56); D050822:Cytokine Receptor gp130