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

Hiroko Nakatsukasa, Dunfang Zhang, Takashi Maruyama, Hua Chen, Kairong Cui, Masaki Ishikawa, Lisa Deng, Peter Zanvit, Eric Tu, Wenwen Jin, Brittany Abbatiello, Nathan Goldberg, Qianming Chen, Lingyun Sun, Keji Zhao, Wanjun Chen

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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 (T H 9 cells) remain incompletely understood. We found here that the DNA-binding inhibitor Id3 regulated T H9 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 T H9 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 T H 9 differentiation.

Original languageEnglish
Pages (from-to)1077-1084
Number of pages8
JournalNature Immunology
Volume16
Issue number10
DOIs
Publication statusPublished - 2015 Sep 18
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Nakatsukasa, H., Zhang, D., Maruyama, T., Chen, H., Cui, K., Ishikawa, M., Deng, L., Zanvit, P., Tu, E., Jin, W., Abbatiello, B., Goldberg, N., Chen, Q., Sun, L., Zhao, K., & Chen, W. (2015). The DNA-binding inhibitor Id3 regulates IL-9 production in CD4 + T cells. Nature Immunology, 16(10), 1077-1084. https://doi.org/10.1038/ni.3252