The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses T H2 differentiation

Makoto Kuwahara, Masakatsu Yamashita, Kenta Shinoda, Soichi Tofukuji, Atsushi Onodera, Ryo Shinnakasu, Shinichiro Motohashi, Hiroyuki Hosokawa, Damon Tumes, Chiaki Iwamura, Veronique Lefebvre, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

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 H2) 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 H2 cytokine, and prevented binding of GATA-3 to this promoter. T H2 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 H2 differentiation and T H2 cell-mediated inflammation.

Original languageEnglish
Pages (from-to)778-786
Number of pages9
JournalNature Immunology
Volume13
Issue number8
DOIs
Publication statusPublished or Issued - Aug 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this