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。虽然严重程度往往 随着年龄的增长，AD可以持续一生。此外，AD严重程度可以是 随后的过敏性疾病，因为60%患有AD的儿童将发展为其他特应性疾病，包括 哮喘因此，通常认为AD是“过敏性行军”向更严重的特应性的第一步 疾病虽然皮肤缺陷和对高Th 2应答的倾向都有助于 AD发病机制中的主要缺陷尚不清楚。慢性病变转化为 Th 1介导的免疫性炎症更具有特征性，尽管触发这种开关的原因尚不清楚。在 在AADCRC的应用中，我们将定义几个导致疾病发生的因素， 加重在项目1中，患者样本和由高Th 2应答引起的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AD所需 发展AD的小鼠模型也将用于定义AD与治疗的同时的作用。 其他特应性疾病的发展。项目2将研究树突状细胞作为介质的贡献 通过检查患者样本中DC群的功能， 以及患有AD的小鼠及其指导Th 2或Th 1依赖性免疫的能力。项目3将 定性和定量地定义来自感染的AD病变的细菌和细菌产物。的作用 脂质介质血小板活化因子（PAF）和Toll样受体在细菌产物介导的 炎症和免疫调节将在体外以及体内使用细胞和 鼠模型。这三个项目得到行政和资源核心的支持， 相互作用和相互关联。本申请的重点，加上互补的背景， 每个项目主任，提供了一个科学的环境，准备在定义快速进展， 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 它不是一种危及生命的疾病，但它是一种严重不适的来源，并可能对社会和 情感发展此外，它是其他过敏性疾病发展的强烈迹象 包括哮喘。这项建议探讨特应性皮炎的发展，以及如何 发展可能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.