Tfh和Tfr细胞参与Graves病甲亢致病机制研究

Graves病甲亢（GD）是一种常见的器官特异性自身免疫性疾病，临床表现复杂，病程长，复发率高。既往研究发现细胞代谢异常通过调控免疫细胞功能与分化参与自身免疫炎症反应，但GD甲亢鲜有这方面的报道。申请人前期研究发现初发GD甲亢患者外周血Tfh细胞增多，Tfr细胞减少，且Tfh/Tfr比例与GD临床指标密切相关；同时GD甲亢患者体内Tfh和Tfr细胞糖酵解代谢增强，但Tfh和Tfr细胞增强的糖酵解代谢在GD甲亢中的具体机制尚不清楚。本项目拟深入研究Tfh和Tfr细胞在GD甲亢病理生理过程中的作用，探索增强的糖酵解代谢对Tfh和Tfr细胞的调节作用。本项目预期研究结果将首次揭示糖酵解代谢通过调控Tfh和Tfr细胞的功能与分化参与GD甲亢的发生，为明确GD的致病网路和寻找新的治疗靶点提供新的理论依据。

Graves’ disease (GD) is a common organ specific autoimmune disease with varied manifestions, long course and high recurrence rate. Previous studies indicated that abnormal cell metabolism participated in a variety of autoimmune inflammatory responses by regulating the function and differentiation of immune cells, but there is a paucity of reports on GD. Our preliminary study found that peripheral blood Tfh cells increased, while Tfr cells decreased in initial GD patients. The Tfh/Tfr ratio was correlated with GD clinical variables; at the same time, the glycolysis of Tfh and Tfr cells in patients with GD increased, however the enhanced glycolysis of Tfh and Tfr cells in GD pathogenesis remains unclear. This present study aims to elucidate the role of Tfh and Tfr cells in the pathogenesis of GD, and the regulatory effect of enhanced glycolysis on Tfh and Tfr cells. The purpose of this study is to clarify the role of glycolysis in the process of GD for the first time, and provide a basis for understanding the pathogenesis netwok of GD and developing novel therapeutic strategy.