September
7,
2016
Dr. Jun Dai
Cutaneous Biology Research Center, Massachusetts General Hospital
Affiliate of Harvard Medical School
Charleston, Massachusetts
(Host: Prof. Ron Burnette)
RORs are ligand-regulated nuclear receptors that can function as transcription factors in regulating inflammation, lipid metabolism, and cellular differentiation of several non-epithelial tissues. Despite of the high expression of RORα in skin epithelium, its functions in this tissue remain unclear. Using gain- and loss-of-function approaches to alter RORα gene expression in human keratinocytes (HKCs), we have found that this transcription factor acts as a positive regulator of epidermal differentiation. Among the 4 RORα isoforms, RORα4 is prominently expressed by keratinocytes in a manner that increases with differentiation. Moreover, increasing the levels of RORα4 in HKCs enhanced the expression of structural proteins associated with early and late differentiation, as well as genes involved in lipid barrier formation. Recent studies have shown that RORα and RORγ are crucial for the development of Th17 cells and type 2 innate lymphoid cells. These types of immune cells are strongly associated with the pathogenesis of certain inflammatory skin diseases such as psoriasis and atopic dermatitis. We found that topical application of the synthetic inverse antagonists of RORα/γ exerted anti-inflammatory effects in the mouse models of irritant dermatitis and atopic dermatitis. Given the regulatory roles of RORα/γ in multiple cell types within the skin tissue, this class of nuclear receptors may represent promising therapeutic targets for various skin disorders.
