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Although the protective effect of M2\u2010like macrophages (M2\u03c6) and their extracellular vesicles (EVs) has been well\u2010documented in other inflammatory diseases, the role of M2\u03c6\u2010derived EVs (M2\u03c6\u2010EVs) in the pathogenesis of ALI\/ARDS remains poorly understood. The present study utilised a mouse model of lipopolysaccharide\u2010induced ALI to first demonstrate a decrease in endogenous M2\u2010like alveolar macrophage\u2010derived EVs. And then, intratracheal instillation of exogenous M2\u03c6\u2010EVs from the mouse alveolar macrophage cell line (MH\u2010S) primarily led to a take up by alveolar macrophages, resulting in reduced lung inflammation and injury. Mechanistically, the M2\u03c6\u2010EVs effectively suppressed the pyroptosis of alveolar macrophages and inhibited the release of excessive cytokines such as IL\u20106, TNF\u2010\u03b1 and IL\u20101\u03b2 both in vivo and in vitro, which were closely related to NF\u2010\u03baB\/NLRP3 signalling pathway inhibition. Of note, the protective effect of M2\u03c6\u2010EVs was partly mediated by miR\u2010709, as evidenced by the inhibition of miR\u2010709 expression in M2\u03c6\u2010EVs mitigated their protective effect against lipopolysaccharide\u2010induced ALI in mice. In addition, we found that the expression of miR\u2010709 in EVs derived from bronchoalveolar lavage fluid was correlated negatively with disease severity in ARDS patients, indicating its potential as a marker for ARDS severity. Altogether, our study revealed that M2\u03c6\u2010EVs played a protective role in the pathogenesis of ALI\/ARDS, partly mediated by miR\u2010709, offering a potential strategy for assessing disease severity and treating ALI\/ARDS.<\/jats:p>","DOI":"10.1002\/jev2.12437","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T23:34:00Z","timestamp":1712705640000},"source":"Crossref","is-referenced-by-count":53,"title":["Extracellular vesicles derived from M2\u2010like macrophages alleviate acute lung injury in a miR\u2010709\u2010mediated manner"],"prefix":"10.1002","volume":"13","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Critical Care 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