Dissecting How Xenobiotics Act as Adjuvants for Oral Allergic Sensitization

项目摘要 自1960年以来，由于未知的原因，食物过敏一直在以指数速度增长。我们假设 被广泛引入现代环境的现代外源性物质可能会引起过敏， 佐剂破坏口服耐受性并引起过敏。该提案将探讨某些非甾体抗- 炎性药物（NSAID）足以引起口腔过敏性致敏。该提案将测试总体 假设佐剂NSAID是异生物质传感器激活剂，核因子红细胞2相关 肠上皮细胞中的NRF 2，其释放IL 33以启动对同时发生的过敏反应。 食物抗原我们将结合遗传学、药理学和质谱学方法， 严格检验这个假设。如果得到证实，我们的工作将对为什么过敏增加产生重大影响。 并可能导致新的公共卫生政策和新的治疗过敏性疾病的管理。

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.