我们前期研究发现，树突状细胞（DCs）在T淋巴细胞介导的肺部炎症中发挥关键作用。但慢性烟草暴露下，DCs调控T淋巴细胞免疫应答特别是负性调节机制尚未清楚。肿瘤微环境中DCs PD-L1过度表达，诱导T淋巴细胞功能耗竭。据此，我们推测慢性烟草暴露下DCs PD-L1表达下调可能是T淋巴细胞过度活化的重要机制。但在烟草所致慢性炎症状态中，DCs PD-L1的表达情况及调控机制尚未见研究报道。本项目拟系统研究慢性烟草暴露条件下，DCs PD-L1的表达情况与T淋巴细胞亚群分化、功能状态的关系；探讨PD-L1在CD103+DCs介导Th1/Tc1细胞免疫反应中的作用；阐明IRF8对CD103+DCs分化、功能的影响和对PD-L1表达的作用及分子机制。本项目的完成将进一步深入了解慢性烟草暴露下肺部炎症放大及肺结构破坏的发病机制，为吸烟相关慢阻肺的防治提供新的治疗靶点与实验依据。

We have previously demonstrated that dendritic cells (DCs) play a pivotal role in T lymphocytes-mediated lung inflammation. However, the mechanisms by which DCs regulating T lymphocyte responses in the context of chronic cigarette smoke exposure, especially the negative regulation, are unclear. Recent studies revealed that PD-L1 was over-expression on DCs in tumor microenvironment, which subsequently drove T cell exhaustion. Therefore, we speculate that the down-regulation of PD-L1 on DCs might represent an important mechanism that T lymphocytes over-activation in the setting of chronic cigarette smoke exposure. However, the expression of PD-L1 on DCs and its modulating mechanisms in chronic inflammation induced by cigarette smoke exposure are largely unknown. In the current study, we sought to evaluate the expression of PD-L1 on DCs and its relation with the differentiation and function of T lymphocyte subsets in the context of chronic cigarette smoke exposure; and explore the role of PD-L1 in CD103+DCs-mediated Th1/Tc1 cell immunity; finally, investigate the role of IRF8 on the development and function of CD103+DCs and its effect on PD-L1 expression. This study could provide insight into the pathogenesis of smoking-related lung inflammation and emphysema; more important, offer new therapeutic targets for the prevention and treatment of smoking-related COPD.