Mesenchymal Stem Cells-derived Exosomes Inhibit Inflammatory Infiltration and Tissue Remodeling in Eosinophilic Chronic Rhinosinusitis

Exosomes generated from mesenchymal stem cells (MSCs-Exos) provide therapeutic promise for inflammatory diseases; however, their function in eosinophilic chronic rhinosinusitis (ECRS) is yet inadequately investigated. This research investigated the immunomodulatory and reparative properties of MSC-derived exosomes in a papain-induced mouse model of ECRS. MSCs-Exos were extracted and analyzed using transmission electron microscopy, NanoSight, and Western blotting. In vivo, intranasal delivery of MSCs-Exos mitigated ECRS symptoms, diminishing sneeze, epithelial hyperplasia, mucus hypersecretion, and collagen deposition. Histopathological and immunohistochemical evaluations demonstrated reduced expression of FXIII-A, Clca1, and iNOS, along with elevated E-cadherin levels, signifying inhibition of epithelial-mesenchymal transition and excessive mucus formation. Flow cytometry revealed that MSCs-Exos rebalanced Th1/Th2/Th17 responses by increasing Th1 (IFN-γ⁺) cell populations and decreasing Th2 (IL-4⁺) and Th17 (IL-17⁺) populations. RNA sequencing and bioinformatic analysis revealed the downregulation of type 2 inflammatory genes (Ccl24, Ccl11) and epithelial remodeling indicators (Clca1, Mmp12), with the enrichment of pathways associated with immune regulation (IL-10 signaling, Treg differentiation) and tissue healing. KEGG pathway analysis further indicated the involvement of IL-17, JAK-STAT, and TNF signaling regulation in the therapeutic effects. MSCs-Exos together alleviate ECRS by reestablishing immunological equilibrium, reducing inflammation, and preventing pathological remodeling, therefore establishing them as a viable cell-free treatment for chronic airway inflammatory conditions.