T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-γ

Qing Yu, Archna Sharma, Sun Young Oh, Hyung Geun Moon, Zulfiquer M. Hossain, Theresa M. Salay, Karen E. Leeds, Hansen Du, Beibei Wu, Marian L. Waterman, Zhou Zhu, Jyoti Misra Sen

Research output: Contribution to journalArticlepeer-review

Abstract

The differentiation of activated CD4+ T cells into the T helper type 1 (TH1) or TH2 fate is regulated by cytokines and the transcription factors T-bet and GATA-3. Whereas interleukin 12 (IL-12) produced by antigen-presenting cells initiates the TH1 fate, signals that initiate the TH2 fate are not completely characterized. Here we show that early GATA-3 expression, required for TH2 differentiation, was induced by T cell factor 1 (TCF-1) and its cofactor β-catenin, mainly from the proximal Gata3 promoter upstream of exon 1b. This activity was induced after T cell antigen receptor (TCR) stimulation and was independent of IL-4 receptor signaling through the transcription factor STAT6. Furthermore, TCF-1 blocked TH1 fate by negatively regulating interferon-γ (IFN-γ) expression independently of β-catenin. Thus, TCF-1 initiates TH2 differentiation of activated CD4+ T cells by promoting GATA-3 expression and suppressing IFN-γ expression.

Original languageEnglish (US)
Pages (from-to)992-999
Number of pages8
JournalNature Immunology
Volume10
Issue number9
DOIs
StatePublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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