Dissecting How Xenobiotics Act as Adjuvants for Oral Allergic Sensitization

项目总结 自1960年以来，由于未知原因，食物过敏一直在以指数级的速度增加。我们假设 被广泛引入现代环境中的现代异生物质可能会起到过敏的作用 打破口服耐受性和引起过敏的佐剂。这项提案将探索某些非类固醇抗肿瘤药物如何 炎症药物(非甾体类抗炎药)足以引起口服过敏反应。这项提案将考验最重要的 假设佐剂非类固醇抗炎药是异种生物传感器的激活剂，核因子红系2相关 肠上皮细胞中的因子2(NRF2)，释放IL33以启动对符合的过敏反应 食物抗原。我们将结合使用遗传学、药理学和质谱学方法来 严格检验这一假设。如果得到证实，我们的工作对过敏症增加的原因有重大影响 并可能导致新的公共卫生政策和管理过敏性疾病的新疗法。

PROJECT SUMMARY Food allergies have been increasing at an exponential rate since 1960 for unknown reasons. We hypothesized that modern xenobiotics that were widely introduced into the modern environment may be acting as allergic adjuvants to break oral tolerance and cause allergy. This proposal will explore how certain non-steroidal anti- inflammatory drugs (NSAIDs) are sufficient for oral allergic sensitization. The proposal will test the overarching hypothesis that adjuvant NSAIDs are activators of the xenobiotic sensor, Nuclear factor erythroid 2-related factor 2 (NRF2), in intestinal epithelial cells, which release IL33 to initiate the allergic response to coincident food antigen. We will use a combination of genetic, pharmacologic, and mass spectroscopic approaches to rigorously test this hypothesis. If confirmed, our work has major implications for why allergies are increasing and could lead to new public health policies and novel therapies for the management of allergic diseases.