Pathogenesis of Atopic Dermatitis

描述(由申请人提供)： 特应性皮炎(AD)是一种常见的过敏性疾病，见于10%-20%的婴儿。虽然严重程度经常 阿尔茨海默病会随着年龄的增长而减少，但会持续一生。此外，AD的严重程度可以预测 随后的过敏性疾病，因为60%患有AD的儿童会发展成其他特应性疾病，包括 哮喘。因此，人们通常认为，AD是迈向更严重特应性的“过敏进行曲”上的第一步 疾病。而皮肤的缺陷和对高Th2反应的易感性都有助于 目前尚不清楚哪种缺陷是AD发病机制中的主要缺陷。慢性皮损转化为 炎症更多地是Th1介导的免疫的特征，尽管触发这种转换的原因尚不清楚。在……里面 本AADCRC申请，我们将定义几个因素，有助于疾病的启动和 病情恶化。在项目1中，患者样本和高Th2反应导致的AD小鼠模型 将用于确定哪些细胞因子和信号通路与AD相关或是AD所必需的 发展。AD的小鼠模型也将被用来定义AD的影响与 其他特应性疾病的发展。项目2将研究树突状细胞作为媒介的作用。 通过检测患者样本中DC群体的功能探讨先天免疫在AD发病中的作用 以及患有阿尔茨海默病及其引导Th2或Th1依赖免疫的能力的小鼠。项目3将 定性和定量定义细菌和感染AD皮损的细菌产品。的作用 细菌产物介导的脂质介质--血小板活化因子和Toll样受体 炎症和免疫调节将在体外和体内使用细胞和 小鼠模型。这三个项目在行政和资源核心的支持下， 互动性和相互关联性。这个应用程序的重点，再加上 每个项目主任都提供了一个科学环境，准备在确定 免疫成分在特应性皮炎中的作用。 特应性皮炎是一种非常常见的过敏性疾病，影响10%-20%的婴儿。虽然它是 它不是一种危及生命的疾病，但会引起极大的不适，并可能对社会和 情感发展。此外，它也是其他过敏性疾病发展的强烈征兆。 晚年，包括哮喘。这项建议研究了特应性皮炎的发展以及如何 疾病的发展可能会影响其他过敏性疾病。

DESCRIPTION (provided by applicant): Atopic dermatitis (AD) is a common allergic disease seen in 10-20% of infants. While severity often diminishes with age, AD can persist throughout life. Moreover, AD severity can be a predictor of subsequent allergic disease as 60% of children who have AD will develop other atopic diseases, including asthma. Thus, it is often thought that AD is the first step on the "Allergic March" towards more severe atopic disease. While both defects in skin and a predisposition towards a hyper-Th2 response contribute towards AD, it is not clear which is the primary defect in the pathogenesis of AD. Chronic lesions convert to inflammation more characteristic of Th1-mediated immunity though what triggers this switch is unclear. In this AADCRC application, we will define several of the factors that contribute to disease initiation and exacerbation. In Project 1, patient samples and a mouse model of AD resulting from hyper-Th2 responses will be used to determine which cytokine and signaling pathways correlate with, or are required for, AD development. The mouse model of AD will also be used to define the effects of AD concurrent with the development of other atopic diseases. Project 2 will examine the contribution of dendritic cells as mediators of innate immunity in the development of AD by examining the function of DC populations in patient samples and mice that have AD and their ability to direct either Th2 or Th1 dependent immunity. Project 3 will qualitatively and quantitatively define bacteria and bacterial products from infected AD lesions. The role of the lipid mediator platelet-activating factor (PAF) and toll-like receptors in bacterial product-mediated inflammation and immunomodulation will be assessed both in vitro as well as in vivo using cellular and murine models. These three projects, supported by an Administrative and Resources Cores, are highly interactive and interrelated. The focus of this application, coupled with the complementary backgrounds of each of the Project Directors, provide a scientific environment poised to make rapid progress in defining the roles of immune components in Atopic Dermatitis. Lay summary-Atopic dermatitis is a very common allergic disorder affecting 10-20% of infants. While it is not a life-threatening disease, it is a source of great discomfort and can have adverse effects on social and emotional development. Additionally, it is a strong indication for the development of other allergic diseases later in life, including asthma. This proposal examines the development of atopic dermatitis and how development may impact other allergic diseases.