Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55170-5 |
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| author | YiLin Chen ChengCheng Yang YuShan Miao DongChen Shi Xiang Li Sen Tian YiFei Zhang ChengFei Xu YuChao Dong ChaoFeng Han Hui Shi Chong Bai |
| author_facet | YiLin Chen ChengCheng Yang YuShan Miao DongChen Shi Xiang Li Sen Tian YiFei Zhang ChengFei Xu YuChao Dong ChaoFeng Han Hui Shi Chong Bai |
| author_sort | YiLin Chen |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-9d789ea2e375420bb55f98653dd50b19 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9d789ea2e375420bb55f98653dd50b192025-01-05T12:37:13ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55170-5Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathwayYiLin Chen0ChengCheng Yang1YuShan Miao2DongChen Shi3Xiang Li4Sen Tian5YiFei Zhang6ChengFei Xu7YuChao Dong8ChaoFeng Han9Hui Shi10Chong Bai11Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, General Hospital of Central Theater Command of Chinese People’s Liberation ArmyDepartment of Respiratory and Critical Care Medicine, No. 906 Hospital of the Chinese People’s Liberation Army Joint Logistic Support ForceDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Histology and Embryology, Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Naval Medical UniversityAbstract 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.https://doi.org/10.1038/s41467-024-55170-5 |
| spellingShingle | YiLin Chen ChengCheng Yang YuShan Miao DongChen Shi Xiang Li Sen Tian YiFei Zhang ChengFei Xu YuChao Dong ChaoFeng Han Hui Shi Chong Bai Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway Nature Communications |
| title | Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway |
| title_full | Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway |
| title_fullStr | Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway |
| title_full_unstemmed | Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway |
| title_short | Macrophage STING signaling promotes fibrosis in benign airway stenosis via an IL6-STAT3 pathway |
| title_sort | macrophage sting signaling promotes fibrosis in benign airway stenosis via an il6 stat3 pathway |
| url | https://doi.org/10.1038/s41467-024-55170-5 |
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