sr1001 and Dermatitis--Atopic

The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin. In the epidermis, SR1001 treatment blocks MC903-induced expression of TSLP and reverses impaired keratinocyte differentiation. SR1001 is also effective in alleviating acute dermatitis triggered by 12-O-tetradecanoylphorbol-13-acetate. Overall, our results suggest that RORα/γ are important therapeutic targets for cutaneous inflammation and suggest topical usage of inhibitory ligands as an approach to treating skin diseases of inflammatory etiology.

Topics: Animals; Cell Differentiation; Cytokines; Dermatitis, Atopic; Dermatitis, Irritant; Disease Models, Animal; Eczema; Epidermis; Female; Inflammation; Keratinocytes; Ligands; Mice; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group F, Member 1; Skin; Sulfonamides; Thiazoles