Fine Particulate Matter Induces Childhood Asthma Attacks via Extracellular Vesicle‐Packaged Let‐7i‐5p‐Mediated Modulation of the MAPK Signaling Pathway

Fine particulate matter less than 2.5 µm in diameter (PM(2.5)) is a major risk factor for acute asthma attacks in children. However, the biological mechanism underlying this association remains unclear. In the present study, PM(2.5)‐treated HBE cells‐secreted extracellular vesicles (PM(2.5)‐EVs) caused cytotoxicity in “horizontal” HBE cells and increased the contractility of “longitudinal” sensitive human bronchial smooth muscle cells (HBSMCs). RNA sequencing showed that let‐7i‐5p is significantly overexpressed in PM(2.5)‐EVs and asthmatic plasma; additionally, its level is correlated with PM(2.5) exposure in children with asthma. The combination of EV‐packaged let‐7i‐5p and the traditional clinical biomarker IgE exhibits the best diagnostic performance (area under the curve [AUC] = 0.855, 95% CI = 0.786–0.923). Mechanistically, let‐7i‐5p is packaged into PM(2.5)‐EVs by interacting with ELAVL1 and internalized by both “horizontal” recipient HBE cells and “longitudinal” recipient‐sensitive HBSMCs, with subsequent activation of the MAPK signaling pathway via suppression of its target DUSP1. Furthermore, an injection of EV‐packaged let‐7i‐5p into PM(2.5)‐treated juvenile mice aggravated asthma symptoms. This comprehensive study deciphered the remodeling of the extracellular environment mediated by the secretion of let‐7i‐5p‐enriched EVs during PM(2.5)‐induced asthma attacks and identified plasma EV‐packaged let‐7i‐5p as a novel predictor of childhood asthma.