组蛋白去乙酰化酶SIRT1负性调控Th9细胞分化  

Histone Deacetylase SIRT1 Negatively Regulates the Differentiation of Interleukin-9-Producing CD4^+T cells

作　　者：Yu Wang Yujing Bi Xi Chen Chunxiao Li Yan Li Zhengguo Zhang Jian Wang Yun Lu Qing Yu Huilin Su Hui Yang 刘光伟[2] 

机构地区：[1]不详 [2]北京师范大学生命科学学院

出　　处：《科学新闻》2017年第4期49-49,共1页Science News

基　　金：国家自然科学基金等项目资助

摘　　要：T细胞是获得性免疫应答的主要效应细胞。T细胞发育分化和功能失调常导致各种重大免疫相关疾病发生。因此，解析T细胞不同亚群的发育分化调控机制，将有助理解免疫相关重大疾病的致病机理和研发免疫防治方法。Distinct metabolic programs support the differentiation of CD4⁺ T cells into separate functional subsets. In this study, we investigated metabolic mechanisms underlying the differentiation of IL-9-producing CD4⁺ T cells (Th9) in allergic airway inflammation and cancerous tumors. We found that histone deacetylase SIRT1 negatively regulated Th9 cell differentiation. A deficiency of SIRT1 induced by either conditional deletion in mouse CD4⁺ T cells or the use of small interfering RNA (siRNA) in mouse or human T cells increased IL-9 production, whereas ectopic SIRT1 expression inhibited it. Notably, SIRT1 inhibited Th9 cell differentiation that regulated anti-tumor immunity and allergic pulmonary inflammation. Glycolytic activation through the mTOR-hypoxia-inducible factor-1α (HIF1α) was required for the differentiation of Th9 cells that conferred protection against tumors and is involved in allergic airway inflammation. Our results define the essential features of SIRT1-mTOR-HIF1α signaling-coupled glycolytic pathway in inducing Th9 cell differentiation, with implications for metabolic reprogramming as an immunotherapeutic approach.

关 键 词：细胞分化 免疫应答 蛋白 重大疾病 T细胞 功能失调 调控机制 防治方法 

分 类 号：Q813[生物学—生物工程]