title: Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation.
abstract: Bcl6 is required for CD4 T cell differentiation into T follicular helper cells (Tfh). In this study, we examined the role of IL-6 in early processes of in vivo Tfh differentiation, because the timing and mechanism of action of IL-6 in Tfh differentiation have been controversial in vivo. We found that early Bcl6(+)CXCR5(+) Tfh differentiation was severely impaired in the absence of IL-6; however, STAT3 deficiency failed to recapitulate that defect. IL-6R signaling activates the transcription factor STAT1 specifically in CD4 T cells. Strikingly, we found that STAT1 activity was required for Bcl6 induction and early Tfh differentiation in vivo. IL-6 mediated STAT3 activation is important for downregulation of IL-2Rα to limit Th1 cell differentiation in an acute viral infection. Thus, IL-6 signaling is a major early inducer of the Tfh differentiation program unexpectedly mediated by both STAT3 and STAT1 transcription factors.
authors: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors: Youn Soo
authors: YS
authors: Choi
authors: Danelle
authors: D
authors: Eto
authors: Jessica A
authors: JA
authors: Yang
authors: Christopher
authors: C
authors: Lao
authors: Shane
authors: S
authors: Crotty
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D051560:Proto-Oncogene Proteins c-bcl-6; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
chemical_list: C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D051560:Proto-Oncogene Proteins c-bcl-6; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor