1241 Extracellular role of granzyme B in vitiligo pathology

Vitiligo is an autoimmune skin disorder clinically characterized by depigmented patches. With therapeutically challenging, a deeper understanding of its pathomechanisms needed to improve current therapeutic approaches. Granzyme B (GzmB), serine protease, has been identified in abundance vitiligo lesions, and genetic polymorphisms GZMB have reported multiple patients. It initially discovered granules CD8+ T cells natural killer cells, secreted from the cytotoxic affects target through internalization via perforin-mediated pores initiate apoptosis. Recent studies shown that other immune non-immune also release GzmB, exhibiting extracellular roles with proteolytic cleavage independent perforin. To elucidate pathological functions GzmB vitiligo, we investigated distribution function both vivo vitro models. In human GzmB-positive were increased upper dermis 5-fold compared healthy controls (p<0.05), 77.9% these being perforin-negative. Sequential staining using toluidine-blue O mast basophils as major cellular sources skin. rhododenol-induced leukoderma guinea pig model, 3-fold number positive observed lesional without co-distribution vitrocytotoxicity assays demonstrated 50 nM decreased viability normal epidermal melanocytes 69.7% vehicle-stimulated ones (p<0.01), but similar concentrations did not show cytotoxicity keratinocytes. Collectively, are skins patients rhododenole-induced pigs perforin production. The suggest perforin, may selectively affect keratinocytes, which possibly contributes melanocyte loss vitiligo.