Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2017 Aug 5

PMID 28774591

Citations 21

Authors

Jun Dai

Min-Kyung Choo

Jin Mo Park

David E Fisher

Affiliations

Soon will be listed here.

Abstract

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.

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