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A comprehensive understanding of the underlying mechanisms of RILI is essential for the development of effective prevention and treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate RILI, we utilized a mouse model that received 12.5\u00a0Gy whole-thoracic irradiation. The evaluation of RILI was performed using a combination of quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), histology, western blot, immunohistochemistry, RNA sequencing, and flow cytometry. Additionally, we established a co-culture system consisting of macrophages, lung epithelial cells, and fibroblasts for in vitro studies. In this system, lung epithelial cells were irradiated with a dose of 4\u00a0Gy, and we employed STING knockout macrophages. Translational examinations were conducted to explore the relationship between STING expression in pre-radiotherapy lung tissues, dynamic changes in circulating CCL2, and the development of RILI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings revealed significant activation of the cGAS-STING pathway and M1 polarization of macrophages in the lungs of irradiated mice. In vitro studies demonstrated that the deficiency of cGAS-STING signaling led to impaired macrophage polarization and RILI. Through RNA sequencing, cytokine profiling, and rescue experiments using a CCL2 inhibitor called Bindarit, we identified the involvement of CCL2 in the regulation of macrophage polarization and the development of RILI. Moreover, translational investigations using patient samples collected before and after thoracic radiotherapy provided additional evidence supporting the association between cGAS-STING signaling activity, CCL2 upregulation, and the development of radiation pneumonitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The cGAS-STING signaling pathway plays a crucial role in regulating the recruitment and polarization of macrophages, partly through CCL2, during the pathogenesis of RILI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-023-04446-3","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T00:01:36Z","timestamp":1693785696000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["STING signaling activation modulates macrophage polarization via CCL2 in radiation-induced lung injury"],"prefix":"10.1186","volume":"21","author":[{"given":"Jianjiao","family":"Ni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengfei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,4]]},"reference":[{"key":"4446_CR1","doi-asserted-by":"publisher","first-page":"2488","DOI":"10.1158\/0008-5472.CAN-10-2820","volume":"71","author":"BC Burnette","year":"2011","unstructured":"Burnette BC, Liang H, Lee Y, Chlewicki L, Khodarev NN, Weichselbaum RR, Fu YX, Auh SL. 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Clin Cancer Res. 2019;25:4343\u201350.","journal-title":"Clin Cancer Res"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04446-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-023-04446-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-023-04446-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T14:15:15Z","timestamp":1700403315000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-023-04446-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,4]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4446"],"URL":"https:\/\/doi.org\/10.1186\/s12967-023-04446-3","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,4]]},"assertion":[{"value":"31 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study adhered to the principles outlined in The Declaration of Helsinki and was approved by the institutional review board of Fudan University Shanghai Cancer Center. Informed consent was waived by the institutional review board due to the retrospective nature of the study. All of mouse experiments have been approved by the Laboratory Animal Ethics Committee of the Fudan University Shanghai Cancer Center and have been performed in accordance with relevant institutions and national guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"590"}}