Tet3介导的表观遗传修饰对CD4+T细胞分化及Th17细胞功能的调控

项目名称： Tet3介导的表观遗传修饰对CD4+T细胞分化及Th17细胞功能的调控

项目编号： No.31600712

项目类型： 青年科学基金项目

立项/批准年度： 2017

项目学科： 生物科学

项目作者： 邵靖

作者单位： 清华大学

项目金额： 20万元

中文摘要： 辅助性T细胞由初始CD4+T细胞分化而来，能分泌特异的细胞因子调控其它免疫细胞功能，是一群对机体免疫应答有重要调控作用的T细胞，也与人类自身免疫性疾病密切相关。Th17是辅助性T细胞的重要亚群，能通过分泌IL-17等促炎性细胞因子促进机体炎症反应的发生，因而在统性红斑狼疮多发性硬化症等自身免疫性疾病的致病机理中起关键作用。因此，辅助性T细胞特别是Th17的分化及功能相关研究成为当前研究热点。近年的研究发现了Tet家族蛋白介导的DNA表观遗传修饰调控新机制，揭示了Tet对胚胎干细胞等多种细胞的细胞分化及功能的关键调控作用，然而对免疫细胞分化及功能的调控还少有研究。本研究将探讨Tet3对CD4+T细胞分化及Th17细胞因子分泌的影响，阐明调节Th17分化及功能的机制，进一步揭示该机制在机体免疫应答及自身免疫性疾病中的作用，并通过与Tet2相关调控机制的比较阐明二者对免疫调控的协同效应及差异。

中文关键词： CD4+T细胞；Th17；Tet3；转录调控；表观遗传修饰

英文摘要： The T helper cells are a type of T cells that plays important roles in the immune system. These cells are differentiated from naive CD4+T cell, and they produce linage specific cytokines to help the activity of other immune cells. In this way, the T helper cells regulate immune responses, and also affect the development of autoimmune diseases. Th17 is a subset of pro-inflammatory T helper cells defined by its production of inflammatory and pro-inflammatory cytokines such as interleukin 17. And Th17 has been proved to have key role in autoimmune and inflammatory disorders. Because of these pathological implications, the research field of the differentiation and function of T helper cells has become a hot field..In the recent years, Tet family protein dependent active DNA demethylation has been identified. And the function of Tet in diverse biological processes including cell differentiation has been revealed. But the function of Tet in the regulation of the differentiation and function T helper cells is not well studied. .In our study, the role of Tet3 in CD4+T cell differentiation will be elucidated. The underlying mechanism related with Tet3 dependent regulation of Th17 differentiation and function will be clarified. We will study the regulation of Tet3 to CD4+T cell differentiation in antigen immunized mice to confirm the former conclusion. And we will also learn the role of Tet3 dependent regulation of Th17 in EAE disease model to elucidate the function of Tet3 in immune response and autoimmune disease. Furthermore, by comparing the effect of Tet3 with Tet2 in the regulation of Th17 differentiation and function, we will elucidate the relation and difference between Tet3 and Tet2-dependent epigenetic regulation of the immune system. Our study will broaden the understanding of Tet dependent epigenetic regulation in immune response and have great implications in the development of drugs for autoimmune diseases targeting epigenetic regulation system.

英文关键词： CD4+T cell;Th17;Tet3;transcription regulation;epigenetic modification