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From the morphological to the transcriptomic characterization of a compromised three‐dimensional in vitro model mimicking atopic dermatitis
Author(s) -
RouaudTinguely P.,
Boudier D.,
Marchand L.,
Barruche V.,
Bordes S.,
Coppin H.,
Roth M.P.,
Closs B.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.14012
Subject(s) - thymic stromal lymphopoietin , proinflammatory cytokine , atopic dermatitis , inflammation , interleukin 20 , immunology , transcriptome , interleukin , spongiosis , tumor necrosis factor alpha , context (archaeology) , filaggrin , biology , loricrin , in vitro , keratinocyte , medicine , cytokine , gene expression , involucrin , interleukin 5 , biochemistry , gene , paleontology
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 .