SIRT4是NAD+依赖的第三类组蛋白去乙酰化酶sirtuins家族成员，其在调控细胞能量代谢中发挥重要作用，但是至今尚未有关于SIRT4调控T细胞代谢并影响其活化功能的报道。本课题组高脂诱导肥胖小鼠的预实验显示：（1）脾细胞及CD4+T细胞中SIRT4表达明显降低，CD4+CD25+(Treg)亚群细胞明显增多（2）基因表达谱分析显示，T细胞亚群代谢活化信号及基因表达明显差异。本项目拟在此研究基础上:（1）利用一系列基础实验探讨SIRT4在T细胞代谢活化信号通路中的作用（2）利用高脂和SIRT4-/-基因工程小鼠等动物模型明确肥胖中SIRT4影响T细胞功能而导致宿主抗病原体免疫应答异常（3）从临床验证SIRT4、T细胞代谢活化及免疫反应之间的关系。旨在阐明SIRT4调控T细胞代谢及功能的分子机制，以及与肥胖者免疫反应能力低下之间的关系，为临床肥胖症感染防治提供理论指导和实验依据。

SIRT4 is a member of the third NAD+ dependent histone sirtuins family, which plays an important role in regulating cell energy metabolism. The metabolism of T cells is closely associated with the function of T cells. But the role of SIRT4 in regulating metabolism of T cells and influencing function of T cells has not yet been reported. In our pre-experiment, it was found that(1) the expression of SIRT4 in spleen cells and CD4 + T cells from high fat diet-induced obese mice was significantly decreased, and(2) the signaling of activation and gene-associated was significantly different in subtype of T cells by analyzing gene expression spectrum of CD4+ T cells from high fat diet-induced obese mice. On the basis of the results, this project is planned: (1) to investigate the effect of SIRT4 on signaling pathway of T cell metabolism and activation; (2) to verify the role of SIRT4 in the function of CD4 + T cell involving in host anti-pathogen immune response; (3) to further clarify the relationship between SIRT4, the metabolism and activation of T cell and immune response from the clinical obesity patient samples. The aim of this project is to exploit the mechanism that SIRT4 regulate the metabolism and function of T cell, and the relationship between this mechanism and low immune response to pathogens infection in obesity host. It will provide theoretical guidance and experimental basis for clinical obesity infection prevention