Characterizing Keratinocyte-Derived Extracellular Vesicles in UVB-Irradiated Murine Skin

UVB radiation is a potent trigger for photosensitive autoimmune diseases, yet the mechanism through which UVB-induced superficial epidermal damage drives deeper systemic inflammation remains poorly understood. Extracellular vesicles (EVs) have emerged as key mediators of UVB-induced immune activation and have also been specifically implicated in the pathogenesis of multiple photosensitive autoimmune diseases, therefore suggesting the possibility that UVB-induced EVs could be involved in driving this systemic inflammation. In this study, C57BL/6 mice were exposed to repeated dorsal UVB irradiation, and dermal tissue was processed to isolate EVs through sequential ultracentrifugation and density-gradient purification. Transmission electron microscopy, ExoView, immunogold labeling, and western blotting confirmed the presence of EVs within the dermis, including those expressing cytokeratin 10, a keratinocyte differentiation marker. UVB-irradiated dermal EVs showed significantly higher cytokeratin 10 expression than sham controls, supporting their keratinocyte origin and demonstrating that EVs can traverse the epidermal-dermal junction. These findings provide direct evidence that UVB triggers the release of keratinocyte-derived EVs into the dermis, where they may serve as vehicles for inflammatory signaling and immune modulation. The identification of cytokeratin 10-positive EVs as mediators of epidermal-dermal crosstalk highlights a potential mechanism linking UVB exposure to systemic autoimmunity and suggests, to our knowledge, a previously unreported therapeutic targets to mitigate photodamage.