ATP6V0d2通过调节酸碱平衡影响Th17细胞代谢、分化和功能的机制

项目名称： ATP6V0d2通过调节酸碱平衡影响Th17细胞代谢、分化和功能的机制

项目编号： No.31470851

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 杨想平

作者单位： 华中科技大学

项目金额： 90万元

中文摘要： 已证实，胞内能量代谢方式可调控T细胞功能亚群分化及功能。Th17细胞是一类重要的效应细胞，主要借助糖酵解途径供能。目前尚不清楚，糖酵解产生乳酸所致微环境酸化的调控机制，及其对Th17细胞分化及功能的影响。申报者前期研究发现，Th17细胞可特征性表达ATP6V0d2（液泡ATP水解酶的一种亚单位），该分子具有调节胞内外质子转运（pH）的功能。申报者据此推测: ATP6V0d2可能通过维持胞质酸碱平衡而影响Th17细胞分化和功能。本项目拟探讨如下科学问题：①Th17细胞表达ATP6V0d2的调控机制；②ATP6V0d2对Th17细胞代谢、分化、增殖、可塑性与功能的影响及其机制；③ATP6V0d2对Th17细胞介导动物自身免疫病的影响及机制。本项目可望从新的角度（能量代谢方式）阐明Th17细胞分化、发育的调控机制，并为探索基于Th17细胞的干预策略提供线索。

中文关键词： Th17；液泡三磷酸水解酶；新陈代谢；自身免疫；转录调节

英文摘要： It has been appreciated that metabolism can regulate the differentiation and functions of CD4 T cells. Th17 cells are an important subset of effector cells, and mainly depend on glycolysis for energy. However, how Th17 cells respond to the high amount of lactate and H+ produced by glycolysis remains incompletely understood. Our preliminary data show that ATP6V0d2 (a subunit of vacuolar ATPase) is specifically induced under multiple Th17 culture conditions, and the main function of V-ATPase is to pump the H+ from the cytosol into the intracellular organella or extracellular matrix. Thus we hypothesised that ATP6V0d2 may govern the differentiation process and functions of Th17 cells via maintaining the intracellular pH homeostasis. This study intends to investigate the following scientific questions: (1) the mechanisms of ATP6V0d2 induction in Th17 cells; (2) the regulation of metabolism, differentiation, proliferation, plasticity and functions of Th17 cells by ATP6V0d2; (3) the roles of ATP6V0d2 in Th17 cell-mediated autoimmune diseases. The study will investigate the regulatory mechanisms of differentiation and functions of Th17 cells by metabolism pathways and related molecules, and the results will shed lights on how to design novel intervention strategies for the treatments of Th17 cells-mediated autoimmune diseases.

英文关键词： Th17;Vacuolar H+ ATPase;metabolism;autoimmunity;transcriptional regulation