Extracellular vesicles derived from M2‐like macrophages alleviate acute lung injury in a miR‐709‐mediated manner

作者：Jie Yang, Xiaofang Huang, Qing Yu, Shibo Wang, Xuehuan Wen, Songjie Bai, Lanxin Cao, Kai Zhang, Shufang Zhang, Xingang Wang, Zhanghui Chen, Zhijian Cai, Gensheng Zhang · 发表于：Journal of Extracellular Vesicles · 年份：2024 · DOI：10.1002/jev2.12437 · 被引用次数：45 · 研究领域：Extracellular vesicles in disease、Inflammasome and immune disorders、Immune cells in cancer

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is characterised by an uncontrolled inflammatory response, and current treatment strategies have limited efficacy. Although the protective effect of M2-like macrophages (M2φ) and their extracellular vesicles (EVs) has been well-documented in other inflammatory diseases, the role of M2φ-derived EVs (M2φ-EVs) in the pathogenesis of ALI/ARDS remains poorly understood. The present study utilised a mouse model of lipopolysaccharide-induced ALI to first demonstrate a decrease in endogenous M2-like alveolar macrophage-derived EVs. And then, intratracheal instillation of exogenous M2φ-EVs from the mouse alveolar macrophage cell line (MH-S) primarily led to a take up by alveolar macrophages, resulting in reduced lung inflammation and injury. Mechanistically, the M2φ-EVs effectively suppressed the pyroptosis of alveolar macrophages and inhibited the release of excessive cytokines such as IL-6, TNF-α and IL-1β both in vivo and in vitro, which were closely related to NF-κB/NLRP3 signalling pathway inhibition. Of note, the protective effect of M2φ-EVs was partly mediated by miR-709, as evidenced by the inhibition of miR-709 expression in M2φ-EVs mitigated their protective effect against lipopolysaccharide-induced ALI in mice. In addition, we found that the expression of miR-709 in EVs derived from bronchoalveolar lavage fluid was correlated negatively with disease severity in ARDS patients, indicating its potential as a mark...