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Immunol."],"abstract":"<jats:p>Radiation-induced lung injury (RILI) is a major dose-limiting toxicity of chest radiotherapy (RT), and its occurrence and development are closely related to the complex role of macrophages. RT significantly modulates the recruitment and functional status of macrophages. In the early stage, macrophages predominantly exhibit a pro-inflammatory M1 phenotype, releasing a large amount of inflammatory factors and exacerbating lung tissue damage. In the late stage, they shift to a pro-fibrotic M2 phenotype, promoting fibroblast activation, extracellular matrix accumulation, and epithelial-mesenchymal transition, thereby facilitating the progression of pulmonary fibrosis. In addition, the metabolic reprogramming induced by RT significantly affects the function of macrophages, manifested by imbalances in glucose, lipid, and amino acid metabolism and mitochondrial dysfunction, further reinforcing phenotypic polarization and functional heterogeneity. This complexity offers diversified strategies for the treatment of RILI by targeting macrophages, including phenotypic regulation, metabolic intervention, delivery systems and cell engineering development, and combination therapy, demonstrating new potential for mitigating RILI. However, the widespread use of immune checkpoint inhibitors has exacerbated the difficulty in preventing and treating RILI, necessitating urgent exploration of effective and safe intervention measures.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1863541","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:50:27Z","timestamp":1784695827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of macrophages in radiation-induced lung injury: from pathological mechanisms to therapeutic targets"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaochi","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University","place":["Jinan, Shandong, 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