The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses T(H)2 differentiation

Nat Immunol. 2012 Jul 1;13(8):778-86. doi: 10.1038/ni.2362.


Sox4 is a transcription factor that regulates various developmental processes. Here we show that Sox4 was induced by TGF-β and negatively regulated the transcription factor GATA-3, the master regulator of function of T helper type 2 (T(H)2) cells, by two distinct mechanisms. First, Sox4 bound directly to GATA-3, preventing its binding to GATA-3 consensus DNA sequences. Second, Sox4 bound to the promoter region of the gene encoding interleukin 5 (IL-5), a T(H)2 cytokine, and prevented binding of GATA-3 to this promoter. T(H)2 cell-driven airway inflammation was modulated by alterations in Sox4 expression. Thus, Sox4 acted as a downstream target of TGF-β to inhibit GATA-3 function, T(H)2 differentiation and T(H)2 cell-mediated inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • DNA-Binding Proteins / antagonists & inhibitors
  • GATA3 Transcription Factor / biosynthesis
  • GATA3 Transcription Factor / metabolism*
  • Interferon-gamma / biosynthesis
  • Interleukin-5 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pneumonia / immunology
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering
  • SOXC Transcription Factors / genetics*
  • SOXC Transcription Factors / metabolism*
  • Signal Transduction
  • Th2 Cells / cytology*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*


  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Interleukin-5
  • RNA, Small Interfering
  • SOXC Transcription Factors
  • Sox4 protein, mouse
  • Transforming Growth Factor beta
  • Interferon-gamma