Tim-3/gal-9信号通路介导Th17/Treg细胞在造血干细胞移植后aGVHD中的调控作用研究

Th17和Treg细胞参与了移植免疫应答，预实验证实在aGVHD患者中两者比例出现失衡。Tim-3表达于Th17和Treg细胞表面，与配体gal-9结合，调节上述两种细胞的功能及比例，但此过程如何调节aGVHD尚不清楚。申请人拟以Tim-3/gal-9为主线，以受其调控的Th17/Treg细胞为切入点，以造血干细胞移植后aGVHD患者为研究对象，通过流式细胞术、ELISA、基因芯片、免疫共沉淀、免疫细胞功能实验和动物模型等方法研究Tim-3+Th17、Tim-3+Treg细胞亚群变化及相关基因、蛋白、细胞因子的表达，并进一步检测体内外阻断后上述指标的变化，阐明Tim-3/gal-9在调节该细胞亚群的机理，探讨该信号异常对aGVHD发生发展的作用，进而为该类疾病的临床干预提供新思路。

Both Th17 and Treg cells participate in immune responses in allogeneic stem cell transplantation(allo-HSCT), and preliminary experiments show the imbalance of Th17/Treg play roles in the process of acute graft-versus-host diseases(aGVHD). Tim-3, expressed in the surface of Th17 and Treg cells, regulates the function of the two cells and adjust the proportion of Th17/Treg by combining with its ligand, gal-9, which is clear, while there is no in-depth study in the biological significance in aGVHD. In this project, we provide Tim-3/gal-9 signal as main line, Th17/Treg cells which is regulated by Tim-3/gal-9 as breakthrough point, aGVHD patients after allo-HSCT as research objects. Through experimental methods including FACS, ELISA, gene chip, immune coprecipitation, functional test of immune cells, and animal model, the expression of Tim3+CD4+IL-17+T, Tim-3+CD4+Foxp3+T subsets, and proteins and cytokins involved are detected. Considering the changes of Th17 cell, Treg cell subsets, the mechanisms of regulatory function by Tim-3/gal-9 signal pathway are clarified, the relationship between the pathway and aGVHD are investigated, hence provide new ideas for clinical interventions in this kind of diseases.