Flaky Tail Mouse Denotes Human Atopic Dermatitis in the Steady State and by Topical Application with Dermatophagoides pteronyssinus Extract
Flaky Tail Mouse Denotes Human Atopic Dermatitis in the Steady State and by Topical Application with Dermatophagoides pteronyssinus Extract
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DOI：
10.2353/ajpath.2010.090957
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发表时间：
2010-05-01
影响因子：
6
通讯作者：
Kabashima, Kenji
中科院分区：
文献类型：
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作者：
Moniaga, Catharina Sagita;Egawa, Gyohei;Kabashima, Kenji
屏障异常是编码微丝蛋白(flaggrin，Flg)基因的一种功能缺失突变，与特应性皮炎(AD)的发生有关，是最近发现的AD发病机制中的一个重要因素。FLAG(Ft)小鼠本质上缺乏微丝蛋白，已被用来研究微丝蛋白在阿尔茨海默病中的作用。然而，flg(Ft)小鼠与人类阿尔茨海默病的相关性需要进一步确定。在本研究中，我们观察了稳定状态下Flg(Ft)小鼠的临床表现，以及它们对外界刺激的皮肤免疫反应，有利于人类AD。在特定的无病原体条件下，大多数Flg(Ft)小鼠出现了与人类AD相似的临床和组织学湿疹皮损，并通过新设计的方法评估了从外到内皮肤屏障功能障碍。此外，皮肤半抗原诱导的接触性超敏反应作为获得性免疫反应的模型和尘螨提取物诱导的皮炎模型在FLG(Ft)小鼠中得到了增强，该模型在生理上与人类AD有关。这些结果表明，Flg(Ft)小鼠基因型有可能成为人类AD中与微丝蛋白突变相对应的AD动物模型。(Am J Pathol2010,176：2385-2393；DOI：10.2353/ajpath.2010.090957)
The barrier abnormality, a loss-of-function mutation In the gene encoding filaggrin (FLG), which is linked to the incidence of atopic dermatitis (AD), is a recently discovered but important factor in the pathogenesis of AD. Flaky tail (Flg(ft)) mice, essentially deficient in filaggrin, have been used to investigate the role of filaggrin on AD. However, the relevancy of Flg(ft) mice to human AD needs to be determined further. In this study, we observed the clinical manifestations of Flg(ft) mice in the steady state and their cutaneous immune responses against external stimuli, favoring human AD. Under specific pathogen-free conditions, the majority of Flg(ft) mice developed clinical and histological eczematous skin lesions similar to human AD with outside-to-inside skin barrier dysfunction evaluated by newly devised methods. In addition, cutaneous hapten-induced contact hypersensitivity as a model of acquired immune response and a mite extract-induced dermatitis model physiologically relevant to a human AD were enhanced in Flg(ft) mice. These results suggest that the Flg(ft) mouse genotype has potential as an animal model of AD corresponding with filaggrin mutation in human AD. (Am J Pathol 2010, 176:2385-2393; DOI: 10.2353/ajpath.2010.090957)