慢性阻塞性肺疾病（COPD）是由于香烟雾或其它毒性烟雾及病原微生物感染等在肺部引起的一种慢性疾病，与机体免疫反应密切相关。COPD患者肺组织自噬和凋亡增强，但机制不太清楚。外源及自身DNA通过cGAS-STING信号通路刺激细胞产生β干扰素。但cGAS-STING信号通路在肺上皮细胞中的功能、与自噬及凋亡的关系和在COPD发生发展中的作用尚未见任何报道。本项目拟用香烟提取物+腺病毒处理cGAS或STING基因功能缺失的肺上皮细胞A549和原代细胞，然后检测细胞β干扰素的产量以及自噬和凋亡的变化；再在cGAS或STING基因敲除或突变小鼠，用香烟雾+腺病毒方法建立COPD动物模型，检测小鼠肺组织β干扰素的产量变化、自噬和凋亡状况的变化、以及COPD病理特征的变化。以期阐明cGAS-STING信号通路在肺上皮细胞中对自噬和凋亡的调控作用，及在COPD疾病发生发展中的作用。

Chronic obstructive pulmonary disease（COPD）is a syndrome caused by inhaling cigarette smoke or other poisonous smoke and pathogen infection, which is characterized by expiratory airflow limitation, deregulated chronic inflammation and emphysematous destruction of the lungs. Immune related signaling pathways play key roles during COPD pathogenesis. Increased autophagy and apoptosis are observed in COPD lungs, but the underlying mechanisms remain unclear. Foreign and self DNA may stimulate cells producing interferon β through cGAS-STING pathway, whose role in the regulation of autophagy and apoptosis in pulmonary epithelial cell and COPD is not known yet. We plan to determine production of interferon β and changes of autophagy and apoptosis after cigarette smoke extract plus viral infection in pulmonary epithelial cells that loss cGAS or STING gene function, and then confirm production of interferon β, changes of autophagy and apoptosis, and analyze pathological alteration in COPD animal models induced by cigarette smoke combining with viral infection in cGAS knockout or STING mutant mice. This study will reveal the function of cGAS-STING pathway against foreign DNA on the regulation of autophagy and apoptosis in pulmonary epithelial cells, and during COPD pathogenesis.