A murine model of psoriasis and atopic dermatitis induced with a combination of systemic IL-23 overexpression and topical application of the vitamin D3 analog MC903

Summary: Abstract Body: Psoriasis and atopic dermatitis (AD) are autoimmune skin diseases with overlapping features. Psoriasis involves IL-17-producing T cells, while AD is mediated by Th2 cytokines like IL-4 and IL-13. Their comorbid presentation in a subset of patients, suggests shared inflammatory mechanisms. We developed a murine model combining systemic IL-23 overexpression with topical MC903 to mimic the dual disease phenotype and investigate shared pathways. Materials and Methods: Using a single IL-23 minicircle DNA (IL-23MC) injection by hydrodynamic delivery via the tail vein and daily topical application of MC903, we induced significant dermatitis in mice. Groups received single or combined treatments, with assessments on days 5, 10, and 15. Histological analysis, cytokine profiling, and flow cytometry were performed. Dose-response experiments evaluated IL-23MC concentrations, and treatment timing effects were analyzed. Results: Combined treatment with IL-23/MC903 resulted in earlier and more severe lesions than single treatment with IL-23 or MC903 alone, accompanied by increased epidermal thickness and Munro microabscesses. Elevated Th17 (IL-17A, IL-22) and Th2 (IL-4, IL-13, TSLP) cytokines were observed, along with high IL-36G levels. Flow cytometry showed increased infiltration of IL-4+ T cells, γδ T cells, and neutrophils. A dose of 6 μg IL-23MC maximized disease severity, while delayed IL-23MC administration enhanced Th1 and Th2 responses. Discussion: This model reproduces key published features of patients with combined psoriasis and AD, highlighting the interplay of Th1, Th2, and Th17 pathways. IL-36G and IL-33 appear central to the disease phenotype. The model provides a platform for studying combination therapies targeting overlapping inflammatory mechanisms. Hideaki Uchida¹, Kaixuan Ren¹, Xuesong Wu¹, Yoshiaki Matsushima¹, Samuel Hwang¹ 1. Dermatology, University of California Davis, Sacramento, CA, United States. Innate Immunity, Microbiology, and Microbiome