Characterization of an animal model of atopic dermatitis

描述（摘自申请）：特应性皮炎是一种慢性， 炎症性皮肤病，影响约20%的3岁至 11.特应性皮炎的患病率正在增加，特别是在 工业化国家。特应性皮炎的特点是皮肤过敏 临床上皮疹，组织病理学上T淋巴细胞和肥大细胞浸润， 血清总IgE升高。虽然通常不致命， 特应性皮炎可引起显著的发病率。临床及实验室资料 对人类患者的研究表明特应性皮炎可能是由 通过Th2型淋巴细胞过度活化超过Th1型淋巴细胞的不平衡， 淋巴细胞，导致Th2偏向的免疫应答。但 一步一步的免疫学事件序列解释了起始， 疾病的进展和维持尚不清楚。此外，委员会认为， 目前还没有可用的特应性皮炎的实验动物模型 一步一步地剖析这些事件。该PI，劳伦斯S。Chan，医学博士，是 作为免疫皮肤病学的研究员在Kevin D.库珀，一个手机 密歇根大学的免疫学家。就目前的建议而言，主要研究者的目标是 表征PI最近创建的转基因（Tg）小鼠模型。 该实验小鼠模型是通过转基因引入 关键Th2细胞因子IL-4对Tg小鼠基底表皮和受影响的 Tg小鼠具有相同的临床、组织病理学、微生物学和 血清学特征为人类特应性皮炎。与可用性 在这个新创建的小鼠疾病模型中，PI现在可以向前移动， 进一步表征该特应性皮炎的实验模型， 具体目标：1）。确定表皮IL-4与肿瘤细胞增殖的相关性， 体内蛋白表达和总血清IgE水平与临床表型。2）。 确定皮肤病变的炎性细胞类型。3）。表征 皮肤损伤的细胞因子谱。通过平行研究 特应性皮炎和免疫学参数，包括病变 炎性细胞和T细胞亚群，损伤性T细胞因子，粘附 分子和总血清IgE，PI旨在逐步描述 免疫事件的发生、进展和维持， 这种疾病PI支持实现这些目标的可能性 过去在这些调查领域的经验和博士的帮助。 斯蒂芬·D米勒，一位经验丰富的细胞免疫学家和合作研究者 本项目描述特应性皮炎的特点， 小鼠疾病模型可能揭示特应性皮炎的发病机制， 人类患者，从而导致最终的靶特异性免疫 治疗患有特应性皮炎的人类患者。

DESCRIPTION (Taken from the application): Atopic dermatitis is a chronic, inflammatory skin disease that affects about 20% children between ages 3 and 11. The prevalence of atopic, dermatitis is increasing, particularly in the industrialized nations. Atopic dermatitis is characterized by pruritic skin rash clinically, T lymphocyte and mast cell infiltration histopathologically, and elevation of total serum IgE serologically. Although usually non-fatal, atopic dermatitis can cause significant morbidity. Clinical and laboratory data from studying of human patients suggests that atopic dermatitis may be caused by an imbalance of excessive activation of Th2-type lymphocytes over Thl-type lymphocytes, resulting in a Th2-biased immune response. However, the step-by-step immunological sequence of events accounting for the initiation, progression, and maintenance of the disease remain unclear. Furthermore, currently there is no available experimental animal model of atopic derrnatitis for dissecting these step-by-step events. The PI, Lawrence S. Chan, M.D., was trained as a fellow in Immuno-dermatology under Dr. Kevin D. Cooper, a cellular immunologist at the Univ. of Michigan. For the current proposal, the PI aims at characterizing a transgenic (Tg) mouse model that the PI has recently created. This experimental mouse model was generated by transgenically introduced critical Th2 cytokine IL-4 to the basal epidermis of Tg mice and the affected Tg mice has identical clinical, histopathological, microbiological, and serological characteristics as human atopic dermatitis. With the availability of this newly created mouse disease model, the PI can now move forward to further characterize this experimental model of atopic dermatitis with the following specific aims: 1). Determining the correlation of epidermal IL-4 in vivo protein expression and total serum IgE levels with clinical phenotype. 2). Determining the inflammatory cell types of skin lesions. 3). Characterizing the cytokine profiles of skin lesions. By parallel studying the natural history of atopic dermatitis and the immunological parameters, including lesional inflammatory cell and T cell subsets, lesional T cell cytokines, adhesion molecules, and total serum IgE, the PI aims at delineating the step-by-step immune events accounting for the initiation, progression, and maintenance of the disease. The likelihood of achieving these aims is supported by the PI's past experience in these areas of investigation and the assistance of Dr. Stephen D. Miller, an experienced cellular immunologist and the coinvestigator of the project. Delineating the characteristics of atopic dermatitis in this mouse disease model may shed light to the pathogenesis of atopic dermatitis in human patients, thereby lead to eventual target-specific immunological treatments for human patients suffering from atopic dermatitis.