Characterization of MC903 induced Atopic Dermatitis-like skin inflammation in mice

Atopic Dermatitis (AD) is a chronic inflammatory skin disease that affects both adults and children worldwide. Symptoms of AD, such as recurrent dry, scaly lesions and intensive pruritus, can become an enormous burden to patients and their caregivers. Animal models are needed to better understand the pathophysiology of AD and for evaluating novel therapeutics. Topically applying MC903 (calcipotriol) on mouse skin has been reported to capture key features associated with AD. In the current study, we conducted a comprehensive characterization of MC903 induced ear skin inflammation in the mouse. An 11 day time course revealed skin thickening starting as early as day 4 and significantly progressing up to day 10. This chronicity was mirrored by increased transepidermal water loss in the ear skin. Histologically, hypervascularization, spongiosis, strong immune cell infiltration and epidermal hyperplasia were observed. The animals also manifested pruritic behaviors. The skin expression of Type 2 and other inflammatory cytokines such as IL‐4, IL‐5, IL‐31, TSLP (peak day 4), IL‐1β, IFNγ, TNFα were typically elevated by day 7 and further increased to day 10. Most of these endpoints were attenuated by administration of a selective JAK1 inhibitor (ABT‐317) or a steroid (Dexamethasone). The observations further the understanding of the utility of MC903 as a preclinical model for AD. Support or Funding Information Disclosures: All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.