Work

An innovative three-dimensional skin model for advancing canine atopic dermatitis research

Year: 2025
Type: article
Abstract: Atopic dermatitis is a chronic, inflammatory, and pruritic skin disease affecting both humans and animals. The pathogenesis of Canine Atopic Dermatitis (CAD) involves a complex interplay of genetic factors, such as skin barrier defects and immune dysregulation, as well as environmental triggers. Identifying the role of individual factors in CAD progression through clinical observational studies in atopic dogs remains challenging. This study aimed to develop an in vitro organoid model that accurately recapitulates the morphological and molecular characteristics of CAD. Canine Primary Epidermal Organoids (cPEOs) were cultured from normal canine keratinocytes and treated with Th2 cytokines (IL-4, IL-13) and TNF-α to mimic atopic skin. Morphological changes in the organoids were assessed through histological analysis and transmission electron microscopy. Molecular markers, including keratins 5 and 10, filaggrin, involucrin, loricrin, tight junction proteins, Ki67 (proliferation), and caspase-3 (apoptosis), were evaluated via RT-qPCR and/or immunostaining. Cytokine treatment induced morphological and molecular characteristics in cPEOs reminiscent of CAD, including epidermal spongiosis and reduced suprabasal keratinocyte differentiation. Th2 cytokines increased keratinocyte proliferation while TNF-α appeared to induce cellular apoptosis within the organoid model. Since these organoids effectively mimic CAD characteristics, they can serve as a valuable model system to delineate the effects of multiple factors involved in the pathogenesis of this condition. Furthermore, this organoid platform could be utilized to identify novel therapeutic approaches and test the efficacy of potential novel treatments. • A canine epidermal organoid model was developed to replicate the structural and functional features of normal dog skin. • Treatment with IL-4, IL-13, and/or TNF-α induced atopic dermatitis-like changes in organoids, including spongiosis and altered keratinocyte differentiation. • IL-4 and IL-13 increased keratinocyte proliferation, while TNF-α primarily induced apoptosis. • This organoid model serves as an in vitro model to delineate the pathogenesis of canine atopic dermatitis. • In future, this platform could be used to develop and test novel therapeutic agents.
Language: English
Subfield: Dermatology
Field: Medicine
Open Access status: hybrid
Estimated APC paid: $3,310
OpenAlex ID: W4416410336
FWCI: 1.642
Cites: 42
Cited by: 2
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