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3岁儿童 11.特应性皮炎的患病率正在增加，特别是在 工业化国家。特应性皮炎以皮肤瘙痒为特征 皮疹临床表现为T淋巴细胞和肥大细胞的组织病理学改变， 血清总IgE升高。尽管通常不会致命， 特应性皮炎可能会导致严重的发病率。临床和实验室数据 对人类患者的研究表明，特应性皮炎可能是 Th2型淋巴细胞过度激活对Th1型淋巴细胞过度激活的失衡 淋巴细胞，导致以Th2为主的免疫反应。然而， 一步一步的免疫顺序的事件说明启动， 疾病的进展和维持仍不清楚。此外， 目前尚无特应性皮炎的实验动物模型。 来剖析这些循序渐进的事件。私家侦探劳伦斯·S·陈，医学博士 在凯文·D·库珀博士的指导下接受免疫皮肤病研究员的培训，库珀是一名细胞 大学的免疫学家。来自密歇根州。就目前的提案而言，PI的目标是 描述了PI最近创建的转基因(TG)小鼠模型。 这个实验性的小鼠模型是由转基因引入的 Th2型细胞因子IL-4对转基因小鼠基底表皮的影响 转基因小鼠具有相同的临床、组织病理学、微生物学和 人类特应性皮炎的血清学特征。与可获得性 在这个新创建的小鼠疾病模型中，PI现在可以向前移动到 进一步描述这个特应性皮炎的实验模型 具体目标有：1)。慢性阻塞性肺疾病患者表皮IL-4水平的相关性研究 活体蛋白表达和血清总IgE水平与临床表型的关系。2)。 确定皮损的炎性细胞类型。3)。描述了 皮肤损伤的细胞因子谱。通过平行研究自然历史， 特应性皮炎和免疫学参数，包括皮损 炎症细胞和T细胞亚群，皮损T细胞细胞因子，黏附 分子和血清总IgE，PI的目的是逐步描绘 免疫事件在脑膜瘤的发生、发展和维持中的作用 这种疾病。实现这些目标的可能性得到了国际和平研究所的支持 过去在这些领域的调查经验和博士的协助。 史蒂芬·D·米勒，一位经验丰富的细胞免疫学家，也是该研究的合作者 项目的一部分。特应性皮炎的特点 小鼠疾病模型可能为特应性皮炎的发病机制提供线索 人类患者，从而导致最终靶点特异性免疫 人类特应性皮炎患者的治疗。

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.