LB1587 Cryptochromes and opsins in human mast cells: putative regulators of their functionality

Abstract

Atopic dermatitis (AD) is the most common inflammatory disease of the skin characterized by defects in keratinocyte differentiation and skin barrier dysfunction. Despite its prevalence, an in vitro,commercial model of AD is not currently available to facilitate basic research and therapeutic development. Using the reconstructed full thickness human epidermal model (EpiDermFT), an inflammatory cocktail comprised of Th2 cytokines was used to induce changes to mimic an atopic dermatitis phenotype. Following treatment with IL-4, IL-13 and IL-31, significant changes in several markers of differentiation and skin barrier integrity were observed, closely resembling AD skin. Histological analysis revealed treatment with IL-4, IL-13, and IL-31 reduced the presence of the stratum granulosum and induced spongiosis in the epidermis. Upregulation of pro-inflammatory mediators, such as IL-8, and down regulation of differentiation markers (keratin 1, keratin 10, involucrin, filaggrin) were observed at both the gene and protein level. These findings demonstrate that treatment of the EpiDermFT tissue model with Th2 cytokines induces a phenotype that is consistent with the hallmarks of AD, including altered differentiation and barrier function. We anticipate that the model described here will be useful for screening and evaluating active ingredients and other molecules used in the treatment of atopic dermatitis. LB1588 Ultraviolet light-induced gasdermin c expression is mediated via trpv1/ calcium/calcineurin/nfatc1 pathway