Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle
Daniela Kovacs, Emanuela Bastonini, Stefania Briganti, Monica Ottaviani, Andrea D’Arino, Mauro Truglio, Lorenzo Sciuto, Marco Zaccarini, Alessia Pacifico, Carlo Cota, Paolo Iacovelli, Mauro Picardo
Abstract
cells to destroy melanocytes. Abnormalities have been described in several cells even in pigmented skin as an expression of a functional inherited defect. Keratinocytes regulate skin homeostasis by the assembly of a proper skin barrier and releasing and responding to cytokines and growth factors. Alterations in epidermal proliferation, differentiation, and lipid composition as triggers for immune response activation in vitiligo have not yet been investigated. By applying cellular and lipidomic approaches, we revealed a deregulated keratinocyte differentiation with altered lipid composition, associated with impaired energy metabolism and increased glycolytic enzyme expression. Vitiligo keratinocytes secreted inflammatory mediators, which further increased following mild mechanical stress, thus evidencing immune activation. These findings identify intrinsic alterations of the nonlesional epidermis, which can be the prime instigator of the local inflammatory milieu that stimulates immune responses targeting melanocytes.