ObjectiveTo investigate the regulatory role of MSC-derived exosomes in obliterative bronchiolitis after lung transplantation. MethodsThe murine lung transplantation model was established with male C57BL/6 mice, and the mice were divided into a sham group (sham, n=6), a surgery group (OB, n=6), and a treatment group (OB+MSC-exo, n=6). The in vitro model was created by stimulating RAW264.7 with lipopolysaccharide+nigericin (LPS+Nigericin), and comprised a PBS group, a LPS+Nigericin group, and a LPS+Nigericin+MSC-exo group. Immunofluorescence and hematoxylin-eosin (HE) staining were used to analyze gasdermin D (GSDMD) expression, as well as lumen stenosis in lung grafts. Bioinformatics methods were employed to predict and screen target gene collagen type V alpha 1 (COL5A1). Q-PCR was used to measure mRNA expression levels of interleukin (IL)-1β, IL-18, IL-6, tumor necrosis factor-α (TNF-α), and COL5A1 in lung grafts and macrophages. Western blot was performed to detect Cleaved-Caspase 1 protein expression in lung grafts and GSDMD protein expression in macrophages. ResultsImmunofluorescence and HE staining revealed that in vivo infusion of MSC-exo reduced GSDMD expression in grafts, ameliorated tracheal epithelial cilia loss and lumen stenosis, and decreased Cleaved-Caspase 1 protein as well as IL-1β and IL-18 mRNA expression. MSC-exo treatment or COL5A1 knockdown reduced IL-1β, IL-18, IL-6, and TNF-α mRNA expression in macrophages, with comparable efficacy. MSC-exo infusion also decreased the number of COL5A1+ cells and mRNA expression levels in lung grafts. ConclusionMSC-derived exosomes alleviate obliterative bronchiolitis after lung transplantation by inhibiting COL5A1.