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However, the underlying molecular mechanisms remain unclear. In this study, it is found that exosomal RNA component of the mitochondrial RNA processing endoribonuclease (Rmrp), derived from type II alveolar epithelial cells (AEC\u2010IIs), drives glycolytic defects and immune tolerance in AMs following cecal ligation and puncture (CLP) sepsis. Targeted depletion of Rmrp in either AEC\u2010IIs or AMs alleviated SII and secondary pneumonia induced by\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    infection 48 h post CLP. Mechanistically, Rmrp interacts with and inhibits the ubiquitination and degradation of the RNA\u2010binding protein zinc finger protein 36 (ZFP36). This results in ZFP36 upregulation, subsequently accelerating the decay of 6\u2010phosphofructo\u20102\u2010kinase\/fructose\u20102,6\u2010bisphosphatase 3 (Pfkfb3\n                    <jats:italic>)<\/jats:italic>\n                    mRNA by binding to its AU\u2010rich elements in the 3\u2032 untranslated region. The degradation of\n                    <jats:italic>Pfkfb3<\/jats:italic>\n                    mRNA leads to impaired glycolysis and suppresses immune responses in AMs after sepsis. Additionally, it is found that exosomal Rmrp levels are correlated with AM immune tolerance and the prognosis of patients with sepsis. These findings highlight the critical role of AEC\u2010II\u2010derived exosomal Rmrp in the pathogenesis of SII and secondary pneumonia. Importantly, the study suggests that exosomal Rmrp may serve as a biomarker for predicting and managing SII in clinical settings.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500376","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T10:11:29Z","timestamp":1762164689000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Type II Alveolar Epithelial Cells Promote Sepsis\u2010Induced Immunosuppression in Alveolar Macrophages via Exosomal lncRNA Rmrp Release"],"prefix":"10.1002","volume":"13","author":[{"given":"Chengxi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Anesthesiology and Pain Research Institute the Second Affiliated Hospital University of South China  Hengyang Hunan 421001 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixia","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Henan Provincial People's Hospital People's Hospital of Zhengzhou University Zhengzhou Henan 450003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pain Medicine The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital)  Dongguan Guangdong 523000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayun","family":"Jia","sequence":"additional","affiliation":[{"name":"Biosafety Level 3 Laboratory Hunan Province Center for Disease Control and Prevention  Changsha Hunan 410005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Human Virology Zhongshan School of Medicine and Key Laboratory of Tropical Disease Control of Ministry of Education Sun Yat\u2010sen University Guangzhou 510275 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Tan","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine the Second Affiliated Hospital, University of South China. 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