B4GALT1介导能量代谢异常导致T细胞焦亡在类风湿关节炎中的作用机制研究

类风湿性关节炎（rheumatoid arthritis，RA）是一种累及周围关节为主的多系统炎症性自身免疫疾病，发病率高，是造成我国劳动力丧失和致残的主要疾病之一。研究表明T细胞能量代谢异常可导致RA炎症反应的增强，但其具体机制仍未阐明。课题组前期研究发现β1,4半乳糖基转移酶1（B4GALT1）高表达可损伤T细胞的能量代谢，并促进细胞焦亡，提示B4GALT1可能通过介导能量代谢异常引发T细胞焦亡促进RA炎症进程。本课题在前期研究基础上，拟首先证实B4GALT1调控细胞内能量代谢对T细胞焦亡的作用，然后探讨B4GALT1调控T细胞经典焦亡通路及IL-1β-IL-1RI炎症环路的具体机制，最后利用小鼠嵌合模型体内分析B4GALT1对T细胞能量代谢、焦亡及RA组织炎症的影响。本研究结果将有望阐明RA的病理新机制，为RA的预防和治疗提供新的理论依据和药物靶点。

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder primarily affecting the peripheral joints，it has a high incidence rate, it is a major cause of productivity loss and disability of our country. Studies have indicated that abnormal energy metabolism of T cell can lead to enhanced inflammatory response in RA. However, its underlying mechanism is still unclear. Our previous study showed that increased β-1,4-galactosyltransferase 1 (B4GALT1) impair energy metabolism of T cell and cause cell pyroptosis, which suggested that B4GALT1-mediated abnormal energy metabolism induce T Cell pyroptosis, and enhanced inflammatory response in RA. On the basis of our previous work, firstly, we intend to verify the specific role of B4GALT1 in regulating energy metabolism on T cell pyroptosis. Secondly, we would explore the specific mechanism of B4GALT1 regulating T cell classical pyroptosis pathway and IL-1β-IL-1RI inflammation feedback loop. Finally, we exploited a chimeric mouse model to test the in vivo role of B4GALT1 in T cell energy metabolism, pyroptosis, and RA tissue inflammation. The results of this study will clarify the new pathogenesis and provide new theoretical basis and drug targets for effective prevention and treatment of RA.