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

Research output: Contribution to journalArticle

38 Citations (Scopus)

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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Interleukin-9
Transforming Growth Factors
Interleukin-4
GATA3 Transcription Factor
GATA Transcription Factors
T-Lymphocytes
Experimental Melanomas
DNA
Helper-Inducer T-Lymphocytes
Genetic Promoter Regions
Immunity
Phosphotransferases
Down-Regulation
Neoplasms
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

Nakatsukasa, H., Zhang, D., Maruyama, T., Chen, H., Cui, K., Ishikawa, M., ... 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

The DNA-binding inhibitor Id3 regulates IL-9 production in CD4 + T cells. / Nakatsukasa, Hiroko; Zhang, Dunfang; Maruyama, Takashi; Chen, Hua; Cui, Kairong; Ishikawa, Masaki; Deng, Lisa; Zanvit, Peter; Tu, Eric; Jin, Wenwen; Abbatiello, Brittany; Goldberg, Nathan; Chen, Qianming; Sun, Lingyun; Zhao, Keji; Chen, Wanjun.

In: Nature Immunology, Vol. 16, No. 10, 18.09.2015, p. 1077-1084.

Research output: Contribution to journalArticle

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, vol. 16, no. 10, pp. 1077-1084. https://doi.org/10.1038/ni.3252
Nakatsukasa H, Zhang D, Maruyama T, Chen H, Cui K, Ishikawa M et al. The DNA-binding inhibitor Id3 regulates IL-9 production in CD4 + T cells. Nature Immunology. 2015 Sep 18;16(10):1077-1084. https://doi.org/10.1038/ni.3252
Nakatsukasa, Hiroko ; Zhang, Dunfang ; Maruyama, Takashi ; Chen, Hua ; Cui, Kairong ; Ishikawa, Masaki ; Deng, Lisa ; Zanvit, Peter ; Tu, Eric ; Jin, Wenwen ; Abbatiello, Brittany ; Goldberg, Nathan ; Chen, Qianming ; Sun, Lingyun ; Zhao, Keji ; Chen, Wanjun. / The DNA-binding inhibitor Id3 regulates IL-9 production in CD4 + T cells. In: Nature Immunology. 2015 ; Vol. 16, No. 10. pp. 1077-1084.
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