2. Academic Validation
  3. The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells

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

  • Nat Immunol. 2015 Oct;16(10):1077-84. doi: 10.1038/ni.3252.
Hiroko Nakatsukasa 1,  Dunfang Zhang 1 2,  Takashi Maruyama 1,  Hua Chen 1,  Kairong Cui 3,  Masaki Ishikawa 4,  Lisa Deng 1,  Peter Zanvit 1,  Eric Tu 1,  Wenwen Jin 1,  Brittany Abbatiello 1,  Nathan Goldberg 1,  Qianming Chen 2,  Lingyun Sun 5,  Keji Zhao 3,  WanJun Chen 1
Affiliations

Affiliations

  • 1 Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
  • 2 State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
  • 4 Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
  • 5 Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
PMID: 26322481 DOI: 10.1038/ni.3252
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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