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The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with \u03b2\u2010glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin\u2010induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. \u03b2\u2010Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with \u03b2\u2010glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of \u03b2\u2010glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury\u2010mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury\u2010mediated disorders.<\/jats:p>","DOI":"10.1002\/advs.202308978","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T01:55:11Z","timestamp":1706320511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Innate Immune Training Initiates Efferocytosis to Protect against Lung Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Yoon\u2010Young","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences University of Ulsan College of Medicine ASAN Medical Center  Seoul 05505 Republic of Korea"},{"name":"Department of Microbiology University of Ulsan College of Medicine ASAN Medical Center  Seoul 05505 Republic of 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