Hormones in allergic disease

摘要 上皮屏障功能障碍被认为是过敏性疾病发生和传播的中心环节。 尽管在位置和组织学上存在差异，但皮肤、气道和肠的上皮通常 作为对环境的关键屏障，提供对病原体的先天防御， 先天性和适应性免疫反应。特应性进行曲，过敏性疾病中的高共病率， 上、下呼吸道过敏性疾病中的粘膜反应，以及 特应性皮炎患者都指出过敏的系统方面。然而，系统机制， 在看似完全不同的过敏性疾病中，驱动常见上皮功能障碍仍然难以捉摸， 明白通过对不同疾病中上皮屏障进行比较生物信息学分析， 对与上皮细胞相关的意外激素失衡进行了惊人的初步观察， 过敏性功能障碍。与这些发现一致，我们检测到循环水平的显著变化， 与健康对照组相比，哮喘和湿疹儿科患者的激素水平，包括 胰岛素血浆水平降低，三碘甲状腺原氨酸（T3）和生长激素水平升高 （GH）.引人注目的是，我们发现食物过敏患者血浆中的激素水平也发生了同样的变化 避免触发食物，不经历过敏性炎症，这表明荷尔蒙的变化可能 在全身水平上，过敏性疾病是一种被忽视但重要的潜在成分。基于 根据我们的初步发现，我们提出了我们的中心假设，即激素水平的系统变化 促进变应性疾病中上皮屏障的局部功能障碍和重塑。我们打算测试一下 该假说具有以下三个具体目标：1）识别应答基因和信号传导 网络在多种过敏性疾病，符合系统发病机制的概念，使用 计算方法; 2）确定过敏个体的全身激素水平是否 改变并与激素响应基因的组织表达相关;和3）测试是否激素 不平衡促进上皮屏障功能障碍，在没有活跃的炎症过程中，在器官型 上皮细胞培养总的来说，这项研究将调查激素变化和 哮喘、特应性皮炎和食物过敏中的上皮功能障碍， 这些疾病的系统性方面，有可能是变态反应领域的变革。

ABSTRACT Epithelial barrier dysfunction has been implicated as central to initiation and propagation of allergic disease. Despite differences in location and histology, the epithelium of the skin, airway, and intestine commonly functions as a critical barrier against the environment, providing innate defense against pathogens and bridging innate and adaptive immune responses. Atopic march, high co-morbidities among allergic diseases, unity of mucosal responses in upper and lower airway allergic disease, and barrier defects in intact non-lesional skin of atopic dermatitis patients all point to a systemic aspect of allergy. However, systemic mechanisms that would drive common epithelial dysfunction in seemingly disparate allergic diseases remain elusive and are not well understood. By conducting comparative bioinformatics analysis of epithelial barriers in different diseases, we made striking preliminary observations about unexpected hormonal imbalances associated with epithelial dysfunction in allergy. In concordance with these findings, we detected significant changes in circulating levels of hormones in pediatric patients with asthma and eczema when compared to healthy controls, including a decrease in plasma levels of insulin and an increase in levels of triiodothyronine (T3) and growth hormone (GH). Strikingly, we found that hormone levels were equally altered in the plasma of food allergy patients avoiding trigger foods and not experiencing allergic inflammation, suggesting that hormonal changes may represent an overlooked but significant underlying component of allergic disease at the systemic level. Based on our preliminary findings, we formulated our central hypothesis that systemic changes in hormone levels promote regional dysfunction and remodeling of epithelial barriers in allergic disease. We propose to test this hypothesis with the following three specific aims: 1) to identify hormone-responsive genes and signaling networks in multiple allergic diseases, consistent with the concept of systemic pathogenesis, using a computational approach; 2) to determine whether systemic levels of hormones in allergic individuals are altered and correlate with tissue expression of hormone-responsive genes; and 3) to test whether hormonal imbalance promotes epithelial barrier dysfunction in absence of active inflammatory process, in organotypic epithelial cultures. Collectively, this study will investigate the connection between hormonal changes and epithelial dysfunction in asthma, atopic dermatitis, and food allergy, which represents an entirely overlooked systemic aspect of these diseases that has potential to be transformative to the field of allergy.