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Atopic Dermatitis Studies through In Vitro Models

机译:通过体外模型进行特应性皮炎研究

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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.
机译:特应性皮炎(AD)是一种复杂的炎症性皮肤病,目前尚未完全了解。表皮屏障缺陷和Th2免疫反应异常被认为在该疾病的发病机理中起关键作用。这些变化之间会发生恶性循环,而其他遗传因素和环境因素会进一步加剧这种恶性循环。为了开发功能性治疗方法,因此需要对疾病的病因进行更深入的研究。近年来,关于重现AD重要特征的体外模型已取得重大进展。但是,由于已经开发了许多模型,因此很难找到合适的实验设置。因此,在本文中,我们回顾了模仿AD特征的体外模型的不同类型。最简单的模型是由免疫细胞或角质形成细胞组成的二维培养系统,而三维皮肤或表皮等效物则构成了显示屏障特性的更复杂的分层组织。在那些模型中,通过挑战具有在AD表皮中过表达的白介素混合物的组织或通过沉默编码表皮屏障蛋白的关键基因的表达来获得AD的标志。还描述了与淋巴细胞共培养或含有AD患者细胞的组织等同物。此外,每种模型都放在其研究环境中,并对获得的主要结果进行简要总结。总之,所描述的体外模型是有用的工具,可以更好地了解AD的发病机理,也可以筛选AD领域的新化合物,这可能将为新的预防或治疗策略开辟道路。

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