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

2009; Nature Portfolio; Volume: 10; Issue: 9 Linguagem: Inglês

10.1038/ni.1762

1529-2916

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

Epigenetics and DNA Methylation

The polarization of naive CD4+ T cells to become T helper type 2 cells requires the transcription factor GATA-3. Sen and colleagues show that T cell antigen receptor signals induce interleukin 4–independent but TCF-1–β-catenin–dependent early expression of GATA-3. 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.