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It is currently urgent to clarify RILI pathogenesis and find safe and effective therapeutical strategy. Transcriptomics of RILI mouse lungs indicate that cellular senescence is substantially involved in RILI pathogenesis, and anti\u2010senescence compounds alleviate RILI and pulmonary inflammatory. Single\u2010cell RNA sequencing and multi\u2010color immunofluorescence demonstrate that type II alveolar epithelial cells (AECIIs) are the main senescent cells, and quantitative proteomics illustrate that tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) is more secreted. Clinical samples also confirms that the plasma levels of TRAIL are significantly increased in RILI patients. Mechanistically, AECII\u2010specific TRAIL knockout (\n                    <jats:italic>\n                      Trail\n                      <jats:sup>f\/f<\/jats:sup>\n                      ;Sftpc\u2010Cre\n                    <\/jats:italic>\n                    ) mice presents reduced cellular senescence and RILI, accompanied by reduced mitophagy. Soluble TRAIL activates the mTOR pathway through death receptor 5 to hinder mitophagy, resulting in impaired mitochondrial accumulation and cellular senescence. Immunoprecipitation mass spectrometry identifies that endoplasmic reticulum (ER)\u2010localized transmembrane molecule TMEM131 interact with TRAIL and mediates its transportation from ER to Golgi through Sec23 homolog A of the coat protein complex II. Interruption of this transportation process led to ER\u2010associated degradation of TRAIL proteins through ubiquitylation. The results indicate the pro\u2010senescent role of TRAIL during RILI pathogenesis and reveals the TMEM131\u2010mediated intricate secretory process of TRAIL.\n                  <\/jats:p>","DOI":"10.1002\/advs.202509973","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:16:34Z","timestamp":1764155794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TMEM131\u2010Mediated Soluble TRAIL Triggered Type II Alveolar Epithelial Cell Senescence in Radiation\u2010Induced Lung Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Linzhi","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pulmonary Oncology Zhongnan Hospital of Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunsheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Oncology Zhongnan Hospital 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