Signal transducer and activator of transcription 4 is required for the transcription factor T-bet to promote T helper 1 cell-fate determination

Immunity. 2008 Nov 14;29(5):679-90. doi: 10.1016/j.immuni.2008.08.017.


Transcriptional regulatory networks direct the development of specialized cell types. The transcription factors signal tranducer and activator of transcription 4 (Stat4) and T-bet are required for the interleukin-12 (IL-12)-stimulated development of T helper 1 (Th1) cells, although the hierarchy of activity by these factors has not been clearly defined. In this report, we show that these factors did not function in a linear pathway and that each factor played a unique role in programming chromatin architecture for Th1 gene expression, with subsets of genes depending on Stat4, T-bet, or both for expression in Th1 cells. T-bet was not able to transactivate expression of Stat4-dependent genes in the absence of endogenous Stat4 expression. Thus, T-bet requires Stat4 to achieve complete IL-12-dependent Th1 cell-fate determination. These data provide a basis for understanding how transiently activated and lineage-specific transcription factors cooperate in promoting cellular differentiation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Chromatin / genetics
  • Chromatin / isolation & purification
  • Gene Expression Regulation*
  • Gene Knockout Techniques
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • STAT4 Transcription Factor / metabolism*
  • T-Box Domain Proteins / metabolism*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Transcription, Genetic
  • Transduction, Genetic


  • Chromatin
  • STAT4 Transcription Factor
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma