UCMSC-derived exosomes ameliorate dry eye disease pathogenesis by modulating neutrophils on Th17/Treg balance

Dry eye disease (DED) is a chronic ocular surface disorder characterized by Th17/Treg cells imbalance, particularly prevalent among elderly females. Current treatment approaches are evolving from merely providing symptomatic relief to targeting immune dysfunction. Mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated the ability to modulate the immune response and promote corneal epithelial cell regeneration in DED. Nonetheless, the precise mechanism through which MSC-Exos exert these effects is not yet fully understood. Consequently, the objective of this study was to explore the mechanisms behind the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) in a murine model of DED. We discovered that UCMSC-Exos stimulated human corneal epithelial cell lines wound healing in vitro. The topical or systemic administration of UCMSC-Exos significantly altered cytokine expression by neutrophils, leading to a reduction in proinflammatory cytokine expression and an increase in anti-inflammatory cytokine expression. This shift in the cytokine profile reestablished the Treg/Th17 cells balance, resulting in decreased inflammation and alleviation of DED symptoms, with younger mice showing more pronounced benefits. These results highlight the potential of UCMSC-Exos as a therapeutic approach for DED that modulates immune dysregulation and enhances ocular surface repair.