The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells

Nature Immunology
Hiroko NakatsukasaWanJun Chen

Abstract

The molecular mechanisms by which signaling via transforming growth factor-β (TGF-β) and interleukin 4 (IL-4) control the differentiation of CD4(+) IL-9-producing helper T cells (TH9 cells) remain incompletely understood. We found here that the DNA-binding inhibitor Id3 regulated TH9 differentiation, as deletion of Id3 increased IL-9 production from CD4(+) T cells. Mechanistically, TGF-β1 and IL-4 downregulated Id3 expression, and this process required the kinase TAK1. A reduction in Id3 expression enhanced binding of the transcription factors E2A and GATA-3 to the Il9 promoter region, which promoted Il9 transcription. Notably, Id3-mediated control of TH9 differentiation regulated anti-tumor immunity in an experimental melanoma-bearing model in vivo and also in human CD4(+) T cells in vitro. Thus, our study reveals a previously unrecognized TAK1-Id3-E2A-GATA-3 pathway that regulates TH9 differentiation.

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Citations

Apr 3, 2016·International Journal of Cancer. Journal International Du Cancer·Aws Abdul-WahidJean Gariépy
Apr 21, 2016·European Journal of Immunology·Tiphaine ParrotNadine Gervois
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Methods Mentioned

BETA
transgenic
immunoprecipitation
ChIP
PMA
FACS
Reverse
PCR
transfection

Software Mentioned

Flow Jo
Genomatix Matinspector

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