Abstract

Atopic dermatitis (AD) is a complex inflammatory skin condition that is not fully understood. Epidermal barrier defects and Th2 immune response dysregulations are thought to play crucial roles in the pathogenesis of the disease. A vicious circle takes place between these alterations, and it can further be complicated by additional genetic and environmental factors. Studies investigating in more depth the etiology of the disease are thus needed in order to develop functional treatments. In recent years, there have been significant advances regarding in vitro models reproducing important features of AD. However, since a lot of models have been developed, finding the appropriate experimental setting can be difficult. Therefore, herein, we review the different types of in vitro models mimicking features of AD. The simplest models are two-dimensional culture systems composed of immune cells or keratinocytes, whereas three-dimensional skin or epidermal equivalents reconstitute more complex stratified tissues exhibiting barrier properties. In those models, hallmarks of AD are obtained, either by challenging tissues with interleukin cocktails overexpressed in AD epidermis or by silencing expression of pivotal genes encoding epidermal barrier proteins. Tissue equivalents cocultured with lymphocytes or containing AD patient cells are also described. Furthermore, each model is placed in its study context with a brief summary of the main results obtained. In conclusion, the described in vitro models are useful tools to better understand AD pathogenesis, but also to screen new compounds in the field of AD, which probably will open the way to new preventive or therapeutic strategies.

Highlights

  • Atopic dermatitis (AD), referred to as atopic eczema, is one of the most common chronic inflammatory skin diseases and the most common form of eczema in childhood

  • To date, published studies highlight the requirement for therapeutic strategies which can target restoration of a functional epidermal barrier or which can inhibit T cells from overproducing cytokines

  • In aforementioned coculture models [106, 107], authors have shown that drugs acting on inflammation, like dexamethasone, tacrolimus, or cyclosporine A, are able to suppress inflammatory cell infiltrates by inhibiting the cytokine production triggered by T cells present in the model

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Summary

Introduction

Atopic dermatitis (AD), referred to as atopic eczema, is one of the most common chronic inflammatory skin diseases and the most common form of eczema in childhood. AD is characterized by dry erythematous lesions and intense pruritus. Acute AD lesions mainly involve the epidermis and typically exhibit spongiosis in the suprabasal epidermal layers when compared to the normal tissue. Spongiosis is due to alteration in cohesion between keratinocytes, resulting in enlarged intercellular spaces suggestive of intercellular edema. Inflammatory infiltrate (predominantly lymphocytes) can be noticed at the epidermal level. Lesional dermis is characterized by a marked perivascular T cell infiltrate, predominantly composed of activated

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