{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:33:11Z","timestamp":1792607591000,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070431"],"award-info":[{"award-number":["82070431"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102272"],"award-info":[{"award-number":["82102272"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100116"],"award-info":[{"award-number":["82100116"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Our previous findings have underscored the role of innate immunity in obliterative bronchiolitis (OB). However, despite the central importance of the cyclic GMP\u2012AMP synthase (cGAS)\/stimulator of interferon genes (STING) signalling pathway in innate immune responses, its specific contribution to OB progression remains largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A murine orthotopic tracheal transplantation model was established to replicate OB pathogenesis. RNA sequencing and single\u2010cell RNA sequencing data were analysed to investigate mechanisms underlying OB. Key molecules of the cGAS\/STING pathway were assessed using immunofluorescence staining. Macrophage\u2010specific <jats:italic>Sting1<\/jats:italic> knockout mice were generated to investigate the role of the cGAS\/STING pathway in OB. Haematoxylin and eosin staining and Masson's trichrome staining were utilised to evaluate allograft stenosis and fibrosis. Immune cell infiltration and cytokine expression were analysed using immunofluorescence staining and qRT\u2010PCR. Flow cytometry was used to characterise splenic T\u2010cell subsets and assess co\u2010stimulatory molecule expression in macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cGAS\/STING pathway was upregulated in macrophages infiltrating allografts. Macrophage\u2010specific <jats:italic>Sting1<\/jats:italic> knockout significantly attenuated alloreactive T\u2010cell responses and alleviated OB. Furthermore, <jats:italic>Sting1<\/jats:italic> deletion reduced the expression of inflammatory marker NOS2, antigen\u2010presenting molecule MHC class II and co\u2010stimulatory molecules (CD80 and CD86) in macrophages. Mechanistically, <jats:italic>Sting1<\/jats:italic> knockout inhibited the production of interferon\u2010\u03b12 (IFN\u2010\u03b12), while the protective effect of macrophage\u2010specific <jats:italic>Sting<\/jats:italic> knockout was reversed by IFN\u2010\u03b12 administration. Importantly, STING inhibition enhanced the allograft tolerance\u2010promoting effects of cytotoxic T\u2010lymphocyte\u2010associated antigen 4\u2010Ig (CTLA4\u2010Ig), leading to the preservation of the airway epithelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that cGAS\/STING signalling pathway exacerbated allograft rejection in an IFN\u2010\u03b12\u2010dependent manner. These findings provide insights into potential novel strategies for prolonging allograft survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>cGAS\/STING signalling pathway was activated in macrophages infiltrating allografts.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>cGAS\/STING signalling pathway in macrophages exacerbated allograft rejection, promoted antigen\u2010presenting ability of macrophages and enhanced alloreactive T\u2010cell responses in an IFN\u2010\u03b12\u2010dependent manner.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>STING inhibition potentiated the therapeutic efficacy of CTLA4\u2010Ig in OB.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70323","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T06:40:28Z","timestamp":1745822428000},"source":"Crossref","is-referenced-by-count":2,"title":["cGAS\/STING signalling in macrophages aggravates obliterative bronchiolitis via an IFN\u2010\u03b1\u2010dependent mechanism after orthotopic tracheal transplantation in mice"],"prefix":"10.1002","volume":"15","author":[{"given":"Junhao","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology 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