Transcription factor STAT3 and type I interferons are corepressive insulators for differentiation of follicular helper and T helper 1 cells

John P. Ray, Heather D. Marshall, Brian J. Laidlaw, Matthew M. Staron, Susan M. Kaech, Joe Craft

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

Follicular helper T (Tfh) cells are required for the establishment of T-dependent B cell memory and high affinity antibody-secreting cells. We have revealed herein opposing roles for signal transducer and activator of transcription 3 (STAT3) and type I interferon (IFN) signaling in the differentiation of Tfh cells following viral infection. STAT3-deficient CD4+ Tcells had a profound defect in Tfh cell differentiation, accompanied by decreased germinal center (GC) B cells and antigen-specific antibody production during acute infection with lymphocytic choriomeningitis virus. STAT3-deficient Tfh cells had strikingly increased expression of a number of IFN-inducible genes, in addition to enhanced T-bet synthesis, thus adopting a T helper 1 (Th1) cell-like effector phenotype. Conversely, IFN-αβ receptor blockade restored Tfh and GC B cell phenotypes in mice containing STAT3-deficient CD4+ Tcells. These data suggest mutually repressive roles for STAT3 andtype I IFN signaling pathways in the differentiation of Tfh cells following viral infection.

Original languageEnglish
Pages (from-to)367-377
Number of pages11
JournalImmunity
Volume40
Issue number3
DOIs
StatePublished - Mar 20 2014

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