LILRB4/CD1d信号通路作为免疫检查点调控PD-L1+Treg亚群介导的T细胞耗竭机制研究

LILRB4蛋白含有免疫检查点共有的ITIMs基序，但其调控T细胞耗竭的机制尚不清楚。我们前期研究发现，LILRB4/CD1D基因的表达与肺癌PD-L1+Tregs的浸润密切相关。蛋白互作网络分析发现LILRB4与CD1d有相互关系。免疫共沉淀验证LILRB4可以直接绑定CD1d，目前未见有关LILRB4/CD1d作为免疫检查点的报道。据此我们提出假说：LILRB4/CD1D作为免疫检查点参与PD-L1+Tregs亚群对T细胞耗竭的调控作用。本课题拟从分子，细胞，组织以及动物水平等多层次明确LILRB4/CD1D参与PD-L1+Tregs免疫调控；并探讨其调控机制；确定LILRB4/CD1D对T细胞免疫耗竭的调控；揭示LILRB4/CD1D通过PD-L1+Tregs调控T细胞免疫应答的作用机制。本项目将提出LILRB4/CD1D作为检查点调控T细胞耗竭这一新视点，为肺癌免疫治疗提供新思路。

LILRB4 protein contains the ITIMs motif shared by immune checkpoints, but the mechanism of regulation in T cell exhausted is unclear. Our previous studies have found that the expression of LILRB4/CD1D gene was related to the infiltration of PD-L1+Tregs in lung cancer. The protein-protein interaction net work analysis showed that LILRB4 was correlated with CD1d. Immunocoprecipitation analysis showed that LILRB4 could binding CD1d. There was no report about LILRB4/CD1d as an immune checkpoint. Therefore, we hypothesize that LILRB4/CD1D as an immune checkpoint in the regulation of T cell depletion by PD-L1+Tregs subpopulation. This project will clarify the role of LILRB4/CD1D in the immune regulation of PD-L1+Tregs at molecular, cellular, tissue and animal levels, and to explore its regulatory mechanism, determine the regulation of LILRB4/CD1D on T cell immune exhaustion, and reveal the mechanism of LILRB4/CD1D regulating T cell immune response through PD-L1+Tregs. This project will present LILRB4/CD1D as a checkpoint to regulate T cell exhausted, which will provide a new idea for immunotherapy of lung cancer.