机构：[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.
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.
第一作者机构：[1]Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
通讯作者：
推荐引用方式(GB/T 7714)：
Nakatsukasa Hiroko,Zhang Dunfang,Maruyama Takashi,et al.The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells.[J].NATURE IMMUNOLOGY.2015,16(10):1077-+.doi:10.1038/ni.3252.
APA：
Nakatsukasa Hiroko,Zhang Dunfang,Maruyama Takashi,Chen Hua,Cui Kairong...&Chen WanJun.(2015).The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells..NATURE IMMUNOLOGY,16,(10)
MLA：
Nakatsukasa Hiroko,et al."The DNA-binding inhibitor Id3 regulates IL-9 production in CD4(+) T cells.".NATURE IMMUNOLOGY 16..10(2015):1077-+
医学