TNF- α and TH2 Cytokines Induced Canine Atopic Dermatitis–like Morphologic and Molecular Characteristics in the Canine Epidermal Organoid Culture System

Atopic Dermatitis (AD) is a chronic inflammatory and pruritic skin disease that affects both human and veterinary patients. Canine atopic dermatitis is prevalent in 27% of the canine population. This frequently encountered disease leads to discomfort and reduced quality of life in affected animals. Our methodology utilizes a well-controlled model system of the canine primary epidermal organoids (cPEOs) derived from normal canine keratinocytes and exhibits morphological characteristics and key marker proteins consistent with normal canine skin. We investigated the direct impact of specific immune mediators, namely IL-4, IL-13 (Th2 cytokines), and TNF-α (a pro-inflammatory cytokine), both individually and in combination, on skin barrier components using this model system. The results demonstrated that cytokines induce CAD-like morphological and molecular characteristics in the canine epidermal organoid system, including epidermal spongiosis and reduced suprabasal epidermal differentiation. Th2 cytokines increased epidermal proliferation and TNF-α appeared to induce cellular apoptosis. These findings indicate that the canine epidermal organoid system holds promise as a valuable tool for understanding the pathogenesis of AD in both humans and veterinary patients and can become a potential platform for assessing individual treatment options or screening drug candidates for canine atopic cases.