From the morphological to the transcriptomic characterization of a compromised three‐dimensional in vitro model mimicking atopic dermatitis

Summary Background Atopic dermatitis ( AD ) is a chronic inflammatory skin disease in which skin barrier function is disrupted. In this AD environment, proinflammatory cytokines are upregulated, promoting a vicious circle of inflammation. Although several three‐dimensional in vitro models mimicking AD have been published, no study has presented a fully characterized and controlled model of AD ‐related inflammation. Objectives To develop and characterize, from the morphological to the molecular level, a compromised reconstructed epidermis ( RE ) mimicking AD ‐related inflammation in vitro . Methods Normal human keratinocytes were used to generate RE , treated or not with an inflammatory cocktail (polyinosinic–polycytidylic acid, tumour necrosis factor‐α, interleukin‐4 and interleukin‐13). Results The inflammatory cocktail induces some modifications observed in patients with AD : (i) it leads to spongiosis; (ii) it alters early and terminal differentiation proteins; (iii) it increases thymic stromal lymphopoietin and interleukin‐8 secretion by keratinocytes and (iv) it results in a specific gene expression pattern. Conclusions The inflammatory context contributes to the morphological, functional and transcriptomic changes observed in AD skin. As a result, this compromised RE model shares some characteristics with those found in AD skin and thus can be used as a relevant tool for screening formulations and drugs for the treatment of AD .