急性移植物抗宿主病 (aGVHD)是allo-HSCT的主要并发症，影响移植的疗效。Tim-3是新型负性调控分子，与Galectin-9结合可下调Th17反应增强Treg细胞功能，介导器官移植的免疫耐受。前期研究发现RH-PBSCT移植后aGVHD患者存在着Treg/Th17失衡，影响机体免疫耐受形成。本项目用流式等方法研究Tim-3/Gal-9在RH-PBSCT中的变化规律，分析其在aGVHD中的作用特点。揭示补充Gal-9激活Tim-3/Gal-9通路下调Th1和Th17应答的机制，减缓aGVHD症状；采用质粒转染、基因编辑、受体阻断等技术，体内外实验激活/阻断Tim-3/Gal-9通路，检测Treg/Th17功能及因子，评价该通路促进Treg的抑制作用，诱导机体免疫耐受，有效防控aGVHD的发生，为寻找以Tim-3/Gal-9信号途径及其上下游分子为靶点的治疗aGVHD提供新策略。

Acute graft-versus-host disease (aGVHD) is one of the major complications and reason of death in allogeneic hematopoietic stem cell transplantation. Tim-3 is a novel negative regulatory molecule. As a novel negative regulatory molecule, Tim-3 binds to Galectin-9 to down-regulate the response of Th17 cells and enhance Treg cell function, playing an important role in autoimmune diseases and organ transplantation. Our previous studies have demonstrated that rapid reconstitution of Treg cells after transplantation can better induce immune tolerance; there were Treg/Th17 imbalance in the patients with severe aGVHD. This study investigated the changes of Tim-3/Galectin-9 in patients with and without aGVHD after RH-PBSCT transplantation, and analyzed the regulation of Tim-3/Gal-9 pathway on Treg/Th17 balance. Therefore, our research group will detecte the expression of Tim-3 in CD4+ (Treg, Th17) and and the cytokines of T cells, by using the plasmid transfection, CRISPR/Cas9 gene editing technology, receptor blocking technology, to validate the immune regulation mechanism of Tim-3/Galectin-9 on T cell and provide the theory basis of its target therapy for aGVHD.