Characterisation and Profiling of Standard Atopic Dermatitis Therapies in a Chronic Dermatitis Murine Model Induced by Oxazolone

Abstract

Atopic dermatitis (AD) is a common inflammatory skin disorder characterised by hypersensitivity to allergens, eczematous lesions and pruritus. The aim of this study was to comprehensively characterise a murine model of dermatitis and assess the similarity with the human disease, as well as to profile clinically relevant AD therapies. Four repeated topical administrations of oxazolone in the auricular skin of sensitised mice induced morphological features compatible with AD, including redness and swelling, as well as histological changes typical of spongiotic (eczematous) dermatitis and increased plasmatic IgE. Additionally, key driver Type 2 cytokines involved in the pathophysiology of the disease, IL-4, IL-13 and IL − 31, were upregulated in the skin, along with cytokines related to Type 1, 17 and 22 responses, which have been reported to be relevant in the chronic stages of the disease. RNA-seq studies in OXA model mice samples validate expression changes obtained by q-PCR and suggest a greater significant similarity with the transcriptomic signature of human AD with respect to psoriasis studies. Oral (cyclosporine, prednisolone and baricitinib) and topical treatments (betamethasone, tacrolimus and crisaborole) were effective inhibiting the induced pathology, as well as modulating the cytokine gene signature of AD. In conclusion, our 4 oxazolone challenges model recapitulates many of the key features of the disease and is responsive to AD standard of care therapies in humans.