From the morphological to the transcriptomic characterization of a compromised three-dimensionalin vitromodel mimicking atopic dermatitis

Abstract

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 invitro models mimicking AD have been published, no study has presented a fully characterized and controlled model of AD-related inflammation. To develop and characterize, from the morphological to the molecular level, a compromised reconstructed epidermis (RE) mimicking AD-related inflammation invitro. 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). 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. 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.