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

Immunity. 2014 Mar 20;40(3):367-77. doi: 10.1016/j.immuni.2014.02.005. Epub 2014 Mar 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Antibody Specificity / immunology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD4 Antigens / genetics
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation* / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Immunoglobulin Class Switching / genetics
  • Interferon Type I / genetics
  • Interferon Type I / metabolism*
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / metabolism
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Knockout
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / deficiency
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / cytology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Transcriptome


  • Antibodies, Viral
  • CD4 Antigens
  • Interferon Type I
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor

Associated data

  • GEO/GSE55596