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

Q Yu, A Sharma, SY Oh, HG Moon, MZ Hossain… - Nature …, 2009 - nature.com
Q Yu, A Sharma, SY Oh, HG Moon, MZ Hossain, TM Salay, KE Leeds, H Du, B Wu…
Nature immunology, 2009nature.com
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 …
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.
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