线粒体丙酮酸代谢对T细胞免疫反应的调节功能研究

获得性免疫反应中的T细胞具有很高的可塑性，可以根据免疫反应环境差异分化成为不同功能的T细胞亚型。T细胞内的代谢反应也随之进行重编程以满足分化时不同的代谢需求。T细胞代谢重编程的调控异常直接影响T细胞功能并导致相关免疫疾病。因此，深入研究T细胞中的代谢调控，不仅可以揭示T细胞可塑性的分子机制，还有助于T细胞免疫治疗新方法的建立。丙酮酸作为糖酵解反应中重要的代谢中间产物，其代谢终点决定了细胞内的代谢特征。然而，细胞如何调节丙酮酸的代谢反应，特别是线粒体内丙酮酸代谢的调控机制及其下游生理功能等并不是十分清楚。在前期研究中我们发现线粒体膜蛋白PGAM5可以特异性的调节线粒体中丙酮酸代谢。通过对PGAM5功能及分子机制的进一步探索，我们希望能够揭示丙酮酸线粒体代谢的全新调控机制，及其对 T细胞分化和抗肿瘤免疫反应的影响；并阐明线粒体代谢、表观遗传调控以及T细胞抗肿瘤免疫反应三者之间相互作用关系。

T cell has high lineage plasticity in the adaptive immune system. Upon encountered various stimulation conditions, T cells will differentiate into specific effector T cells with distinctive phenotype, and meanwhile, the metabolic pathways inside T cells will also reprogram to fit for the vast metabolic demand during differentiation. Further investigations on the T cell metabolic reprogram will not only improve our understanding of T cell plasticity but also help us with new immunotherapy methods. Pyruvate is an important metabolite generated in glycolysis. Its final metabolic pathway determines the cellular characteristic of cellular metabolism. However, the detailed regulation mechanism of mitochondrial pyruvate metabolism has not been clarified. Our previous study indicated that mitochondrial membrane protein PGAM5 regulates the pyruvate metabolism in mitochondria. By further investigating the function of PGAM5, we will illuminate the key role of mitochondrial pyruvate metabolism during T cell differentiation and anti-tumor immune response. Our work will also build up links between mitochondrial metabolism, epigenetic regulations, and T cell immunity.