Stat6 in Atopic Dermatitis

特应性皮炎（AD）是过敏性表型的常见表现。以红斑为特征， 皮炎、肿胀和荨麻疹，特应性皮炎可能是随后特应性表型的早期指标。在 至少有一半被诊断患有特应性皮炎的婴儿将发展为随后的特应性疾病，例如 嗜酸性粒细胞性食管炎、食物过敏、过敏性鼻炎和过敏性哮喘。然而， 特应性皮炎和这种疾病对随后的过敏表型的贡献仍然很大程度上是未知的。 不清楚Th 2细胞，即分泌IL-4、IL-5、IL-13和其他细胞因子的T细胞，在肿瘤的发展中是至关重要的。 特应性疾病IL-4通过激活信号转导子促进Th 2细胞的发育， 转录状态激活器。State缺陷的小鼠具有Th 2免疫力的普遍降低， 哮喘和嗜酸性食管炎的模型极大地减少了疾病。Th 2水平升高 这些反应通常与特应性皮炎的发生有关。然而，缺乏一个模型， 严格依赖于Th 2免疫的特应性皮炎阻碍了对 AD患者Th 2细胞我们最近开发了一种转基因小鼠， （Stat 6VT），导致超Th 2表型。这些老鼠倾向于发展一种 无特定病原体环境中的特应性皮炎表型。此外，Stat 6VT转基因小鼠 在IL-4缺乏的背景下不发生疾病，支持在这种情况下需要Th 2免疫。 模型该项目的总体目标是确定Th 2效应细胞因子在特应性模型中的作用。 并确定在患者样本和我们的小鼠模型中，特应性皮炎 发病机制影响免疫反应，并可能有助于随后的发展， 特应性疾病我们的假设是Th 2偏斜的免疫应答倾向于特应性 皮炎并增加随后过敏反应的风险。这将在三个目标中进行测试：1， 特应性贫血婴儿特异性T细胞群中细胞因子分泌和状态激活的定义 2.确定StatBVT转基因小鼠中特应性皮炎发生所需的效应子。 小鼠;和3，确定特应性皮肤病在随后的特应性疾病易感性中的作用，使用 动物模型这些目的的结果将更好地定义Th细胞在特应性免疫应答产生中的作用。 皮炎和随后的过敏性疾病。

Atopic dermatitis (AD) is a common manifestation of the allergic phenotype. Characterized by erythema, pruritis, swelling and hives, Atopic Dermatitis can be an early indicator of subsequent atopic phenotypes. At least half of infants diagnosed with Atopic Dermatitis will develop subsequent atopic disease, such as eosinophillic esophagitis, food allergy, allergic rhinitis and allergic asthma. However, the pathogenesis of Atopic Dermatitis and the contribution of this condition to subsequent allergic phenotypes are still largely unclear. Th2 cells, T cells that secrete IL-4, IL-5, IL-13 and other cytokines are critical in the development of atopic diseases. IL-4 promotes the development of Th2 cells by activation of the Signal Transducer and Activator of Transcription State. Mice deficient in State have a general decrease in Th2 immunity and in models of asthma and eosinophilic esophagitis have greatly diminished disease. Increased levels of Th2 responses are often associated with the development of Atopic Dermatitis. However, the lack of a model of Atopic Dermatitis that is strictly dependent upon Th2 immunity has hampered a more detailed analysis of Th2 cells in AD. We have recently developed transgenic mice expressing a constitutively active State (Stat6VT) in T cells resulting in a hyper-Th2 phenotype. These mice are prone towards developing an Atopic Dermatitis phenotype in a specific pathogen free environment. Moreover, Stat6VT transgenic mice on an IL-4-deficient background do not develop disease, supporting the requirement forTh2 immunity in this model. The overall goal of this project is to determine the role of Th2 effector cytokines in a model of Atopic Dermatitis and determine how, in both patient samples and in our mouse model, Atopic Dermatitis pathogenesis affects immune responses and might contribute towards the development of subsequent atopic diseases. Our hypothesis is that a Th2 skewed immune response is predisposed towards atopic dermatitis and increases the risk of subsequent allergic responses. This will be tested in three Aims: 1, Define cytokine secretion and State activation in specific T cell populations from infants with Atopic Dermatitis; 2, Define the effectors required for the development of Atopic Dermatitis in StatBVT transgenic mice; and 3, Define the role of Atopic Dermatitis in predisposition towards subsequent atopic diseases using animal models. The results of these Aims will better define the role of Th cells in the generation of Atopic Dermatitis and subsequent allergic diseases.