042 Epidermal loss of RORα accelerates skin inflammation in a mouse model of atopic dermatitis

One of the most common skin diseases is atopic dermatitis (AD), a chronic inflammation featuring barrier dysfunction and immune dysregulation. Previously, we reported that nuclear orphan receptor RORα was highly expressed in epidermis human positively regulated expression barrier-related genes, including filaggrin, keratinocytes. In contrast, downregulated AD lesions. We then aimed to evaluate vivo function regulating pathogenesis, using newly generated mice with epidermis-specific Rora knockout (RoraΔepi) an mouse model induced by MC903. observed MC903-triggered ear thickening greatly accelerated enhanced RoraΔepi compared their wild-type littermates. On day 11, displayed severe symptoms, scaling, excoriation, histological features epidermal hyperplasia heavy dermal infiltrations (of eosinophils, neutrophils, macrophages). addition, found earlier onset be associated marked reduction keratin 10 filaggrin not higher production TSLP, key cytokine for initiation this model. These results substantiate importance suppressing development it functions at least part through keratinocyte differentiation function. Further mechanistic studies should help uncover potential as novel therapeutic target other related dysfunction.