July
31,
2023
Xiangmei Hua, Pharmaceutical Sciences graduate student (Jun Dai Research Group), will be defending her PhD research thesis:
The intact skin barrier is essential for the maintenance of human body homeostasis, functioning in limiting water loss, regulating body temperature, and protecting the body from various environmental insults like chemicals and pathogens. The retinoic acid receptor-related orphan receptor α (RORα), which is highly expressed in the epidermis of normal skin, is a critical regulator in diverse physiological processes, including metabolism, circadian rhythm, and inflammation. Despite previous reports highlighting the downregulation of RORα in skin lesions of several inflammatory skin diseases and the positive regulatory functions of RORα in the expression of several differentiation markers and skin barrier-related genes in human keratinocytes, in vivo roles of RORα in skin remains largely unknown.
In this defense, I will present the findings of RORα in skin barrier development and barrier-associated allergic skin inflammation. By utilizing epidermis specific RORα deletion mice (RoraEKO), we found that RORα was essential for epidermal development and skin barrier functions. Histological, biochemical, and multi-omics analysis demonstrated that depletion of epidermal RORα dysregulated epidermal differentiation, keratinization process, and lipid metabolism. Moreover, we determined that loss of epidermal RORα significantly intensified the symptoms of allergic contact dermatitis-like reactions induced by Oxazolone and atopic dermatitis-like symptoms triggered by MC903. Collectively, our findings substantiated the crucial roles of RORα in suppressing the progression of allergic skin inflammation by maintaining epidermal barrier functions. Therefore, developing novel therapeutic approaches that regulate RORα activity holds promising potential in the treatment of diverse inflammatory skin disorders, such as allergic contact dermatitis and atopic dermatitis.
