慢性阻塞性肺病（COPD）是第四大致死性疾病，吸烟是其发病主要因素。吸烟刺激肺部免疫细胞产生促炎因子IL-1β等激活炎症反应是COPD发病的重要机制。IL-38是IL-1家族成员，可促进人树突细胞炎症因子分泌，其基因多态性与自身免疫病密切相关，但IL-38是否调控COPD发病仍无研究涉及。我们前期研究发现：①IL-38可促进小鼠树突细胞炎症因子分泌②COPD发病小鼠肺部IL-38上调③树突细胞通过诱导Th17免疫反应促进COPD发病。据此，IL-38可能通过激活树突细胞调控COPD发病。本项目拟结合吸烟诱导小鼠COPD发病模型，以及体外分化及共培养、重组蛋白、中和抗体呼吸道滴注、树突细胞过继性转移等手段，深入探讨IL-38如何调节树突细胞活化、调控T细胞分化的能力以及如何调节树突细胞在COPD发病中的致病性。项目成果将加深对IL-38调控COPD发病机理的认识，为COPD的治疗提供依据。

COPD is the fourth leading cause of death worldwide. Smoking is the major risk factor for COPD. Smoking induced secretion of proinflammtory cytokines (such as IL-1β) from leukocytes has been recognized as important underlying mechanism for COPD pathogenesis. Notably, an IL-1 family member, IL-38, was reported to promote proinflammatory cytokine secretion in human peripheral blood mononuclear cell-derived dendritic cells (DCs). The polymorphism of IL-38 has been shown to be associated with autoimmune diseases. However, whether IL-38 regulates COPD pathogenesis remains unknown. We have found that: ① IL-38 promotes proinflammtory cytokine production in mouse bone marrow-derived DCs; ② IL-38 is upregulated in the lung of mice with smoking induced COPD; ③ DC-mediated autoimmune response is required in smoking induced COPD. Thus, IL-38 probably promotes COPD progression through activating DCs. Our project aimed to investigate the mechanisms by which IL-38 regulates DC function and DC mediated autoimmune responses in smoking induced COPD. The method of in vitro cell differentiation, recombinant protein or neutralizing antibody intratracheal administration and adoptive transfer of DCs will allow us to understand the regulatory effect of IL-38 on DC induced autoimmune responses in COPD. The result will provide important theoretical basis for prevention and therapeutics of COPD.