title: Transcription factor STAT3 and type I interferons are corepressive insulators for differentiation of follicular helper and T helper 1 cells.
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(+) T cells 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(+) T cells. These data suggest mutually repressive roles for STAT3 and type I IFN signaling pathways in the differentiation of Tfh cells following viral infection.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Ray
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Marshall
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Laidlaw
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Staron
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kaech
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: joseph.craft@yale.edu.
authors.forename: Joe
authors.initials: J
authors.lastname: Craft
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D000914:Antibodies, Viral; D015704:CD4 Antigens; D007370:Interferon Type I; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor