慢性阻塞性肺疾病（COPD）严重危害全球人类健康，其发病机制尚未完全阐明。烟草诱发的气道炎症是COPD核心机制之一。T细胞被认为是控制气道炎症的关键，但其机制并不清楚。研究证据表明PD-1/PD-L1信号通路参与调控T细胞功能及代谢，同时参与COPD发生及发展。申请人在前期发现IRAK-M，TLRs受体负性信号通路，通过Th17/Treg平衡反而加重亚急性香烟烟雾诱导小鼠肺部炎症，相关成果已发表SCI论文，但其深入机制目前尚不明确。我们预实验结果证实IRAK-M缺失导致糖代谢及PD-1/PD-L1信号通路异常。我们推测IRAK-M可能通过PD-1/PD-L1信号通路靶向T细胞功能及代谢。本项目结合体内、体外模型，从组织、细胞、动物三个层次展开解析IRAK-M发挥免疫调节的方式和免疫代谢机制。通过该项目进一步深入吸烟造成的免疫炎症和肺部损伤机制，为COPD患者治疗提供新的治疗靶点和思路。

Chronic obstructive pulmonary disease (COPD) is a serious disease in the world.However, its mechanism is not completely elucidated. Tobacco-induced airway inflammation is one of the core mechanisms of COPD.T cells are thought to be key to controlling airway inflammation.Recently, abnormal immunomodulatory mechanism of COPD has been focused. A large body of research shows that the PD-1/PD-L1 signaling pathway is involved in the regulation of T cell function and metabolism, as well as the pathogenesis of COPD. In the early stage, we found that IRAK-M,the negative regulator of TLRs pathways, aggravate lung inflammation induced by subacute cigarette smoke in mice through Th17/Treg balance, but the in-depth mechanism is still unclear.Our preliminary results confirmed that IRAK-M deficiency result in abnomal expression of glucose metabolism and PD-1/PD-L1 pathyway. We speculate that IRAK-M may regulate T cell function and metabolism through the PD-1/PD-L1 signaling pathway.On this basis, combined with in vivo and in vitro models, this project intends to explore immunoregulatory mechanism mediated by IRAK-M through T cells differentiation and metabolism.