Dissecting How Xenobiotics Act as Adjuvants for Oral Allergic Sensitization

点击翻译按钮获取中文摘要

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.