YiLin Chen: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
ChengCheng Yang: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
YuShan Miao: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
DongChen Shi: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Xiang Li: Department of Respiratory and Critical Care Medicine, General Hospital of Central Theater Command of Chinese People's Liberation Army, Wuhan, China.
Sen Tian: Department of Respiratory and Critical Care Medicine, No. 906 Hospital of the Chinese People's Liberation Army Joint Logistic Support Force, Ningbo, China.
YiFei Zhang: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
ChengFei Xu: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
YuChao Dong: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
ChaoFeng Han: Department of Histology and Embryology, Naval Medical University, Shanghai, China. hcf@immunol.org. ORCID
Hui Shi: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China. Shihui@smmu.edu.cn. ORCID
Chong Bai: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai, China. Chongbai@smmu.edu.cn. ORCID
Acute and chronic inflammation are important pathologies of benign airway stenosis (BAS) fibrosis, which is a frequent complication of critically ill patients. cGAS-STING signalling has an important role in inflammation and fibrosis, yet the function of STING in BAS remains unclear. Here we demonstrate using scRNA sequencing that cGAS���STING signalling is involved in BAS, which is accompanied by increased dsDNA, expression and activation of STING. STING inhibition or deficiency effectively alleviates tracheal fibrosis of BAS mice by decreasing both acute and chronic inflammation. Macrophage depletion also effectively ameliorates BAS. Mechanistically, dsDNA from damaged epithelial cells activates the cGAS-STING pathway of macrophages and induces IL-6 to activate STAT3 and promote fibrosis. In summary, the present results suggest that cGAS-STING signalling induces acute inflammation and amplifies the chronic inflammation and tracheal fibrosis associated with benign airway stenosis, highlighting the mechanism and potential drug target of BAS.
