类风湿关节炎（RA）是高度致残的自身免疫病。滤泡辅助性T细胞(Tfh)和滤泡调节性T细胞(Tfr)二者相互作用和调控机制是免疫学的前沿科学问题，Tfh/Tfr平衡是RA淋巴生发中心形成及自身抗体产生的关键。我们前期证实RA中Treg、Tfr细胞绝对计数降低，且与病情活动相关，低剂量IL-2显著增加Treg细胞，重建免疫耐受。但未知IL-2是否增加Treg定向转化的Tfr？mTOR是影响Tfh、Tfr细胞分化的重要因素，IL-2可能通过PI3K/AKT/mTOR通路调节Tfh/Tfr平衡，具体作用位点尚不清楚。据此，本研究予单细胞测序技术探寻低剂量IL-2调控RA患者Tfh/Tfr平衡的具体机制，以及Tfh、Tfr分化过程中不同的细胞内信号如何动态激活和调节mTOR，阐明Tfh/Tfr失衡与RA自身抗体产生及滑膜炎进展的关系，为低剂量IL-2恢复RA患者免疫耐受的新治疗思路提供理论依据。

Rheumatoid arthritis (RA) is a highly disabling autoimmune disease. The interaction and regulation mechanism of both follicular T (Tfh) cells and follicular regulatory T (Tfr) cells are important frontier scientific issues in immunology. And Tfh/Tfr balance may play a critical role in the formation of lymphoid germinal center and the production of autoantibodies. Our previous research has revealed that there are lower absolute counts of Treg and Tfr cells in correlation with disease activity in RA, and low-dose IL-2 can significantly increase Treg cells so as to restore immune tolerance. However, whether IL-2 can promote orientated transformation from Treg cells to Tfr cells remains unclear. In view of the impact of mTOR on the differentiation of Tfh and Tfr cells, IL-2 may regulate Tfh/Tfr balance through the PI3K/AKT/mTOR pathway in which the specific sites are not definite. Accordingly, this study will explore the specific signaling pathways regulated by low-dose IL-2 in the balance of Tfh/Tfr, and how different intracellular signals activate mTOR dynamically during the differentiation of Tfh and Tfr cells utilizing single cell sequencing technology. We also expound the relationship between Tfh/Tfr imbalance and autoantibodies production as well as synovitis development in RA. It is expected to provide a theoretical basis for the new treatment of low-dose IL-2 to restore immune tolerance in RA patients.