PD-1/PD-L1通路介导T淋巴细胞影响巨噬细胞极化参与血管狭窄作用机制研究

炎症反应在血管损伤后狭窄过程起关键作用，T淋巴细胞和巨噬细胞均参与损伤后内膜增生过程。PD-1/PD-L1作为新的免疫治疗靶点，可调节T细胞等免疫细胞的活性。课题组前期研究发现血管损伤后PD-1表达升高，应用PD-1/PD-L1抑制剂后CD8+T细胞增加，新生内膜增生受到抑制，提示PD-1/PD-L1参与损伤后内膜增生过程，但其机制尚不清楚。本项目拟以PD-1/PD-L1为干预靶点，通过体内、体外实验，细胞学、组织学和动物水平检测血管损伤后微环境中T淋巴细胞、巨噬细胞表型变化、IFN-γ等细胞因子和趋化因子的水平变化以及相关通路的调控情况，探究PD-1/PD-L1在血管损伤后对T淋巴细胞和巨噬细胞极化的调节，了解免疫微环境与血管壁细胞的交互作用，探索针对PD-1/PD-L1通路的有效干预手段，为预防和治疗损伤后血管狭窄提供新思路。

Inflammation plays a key role in stenosis after vascular injury, both lymphocytes and macrophages are involved in neointimal hyperplasia. As a new immunotherapy target, PD-1/PD-L1 can regulate the activity of immune cells, such as T cells. Our previous studies showed the expression of PD-1 was increased after vascular injury. After application of PD-1/PD-L1 inhibitor, the percentage of CD8+T cells was increased, and the neointimal hyperplasia was suppressed. These results suggest that PD-1/PD-L1 may be participated in the process of neointimal hyperplasia while the specific role of PD-1/PD-L1 has not yet been elucidated. This project intends to use PD-1/PD-L1 as the intervention target to detect the phenotypic changes of T lymphocytes and macrophages, the levels of cytokines and chemokines such as IFN-γ and the regulation of related pathways in the microenvironment after vascular injury at the cytology, histology and animal levels through in vivo and in vitro experiments. The purpose of this project is to investigate the regulatory effect of PD-1/PD-L1 on T cells and macrophages polarization after vascular injury, to understand the interaction between immune microenvironment and vascular wall cells, so as to provide a potential therapeutic target for the prevention and treatment of vessels stenosis after vascular injury.