Dissecting How Xenobiotics Act as Adjuvants for Oral Allergic Sensitization

剖析异生素如何作为口腔过敏致敏佐剂

基本信息

批准号：
10409840
负责人：
Andrew Wang
金额：
$ 56.46万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-24 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10409840
关键词：
Acetaminophen Adjuvant Affect Allergic Allergic Disease American Analgesic and Antipyretic Analgesics Antigens Cell Nucleus Cells Chemical Structure Chemicals Child Cholera Toxin Cysteine Data Dendritic Cells Development Dissection Dose Drug usage Environment Environmental Exposure Epithelial Cells Erythroid Etiology Exposure to Fatty acid glycerol esters Food Food Hypersensitivity Food Preservatives Genetic Health Policy High Prevalence Human Hydroquinones Hypersensitivity Ibuprofen Immune response Incidence Ingestion Intestines Knock-out Lead Link Mediating Medicine Modeling Modernization Mus Non-Steroidal Anti-Inflammatory Agents Nuclear Oral Ovalbumin PTGS2 gene Pathway interactions Persons Pharmaceutical Preparations Pharmacology Predisposition Prevalence Process Production Property Public Health Role Severities Signal Transduction Source Specificity Testing Time Work Xenobiotics adduct allergic response dosage food antigen food consumption gut microbiome intestinal epithelium man microbiota novel novel therapeutics nuclear factor-erythroid 2 oral tolerance receptor sensor urban setting

项目摘要

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.

项目摘要自1960年以来，出于未知原因，食物过敏一直以指数率的速度增加。我们假设广泛引入现代环境的现代异生物学可能是过敏的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抗炎症药（NSAIDS）足以进行口服过敏敏化。该提案将测试总体假设辅助NSAIDS是异生物传感器，核因子2相关的激活因子因子2（NRF2），在肠上皮细胞中，释放IL33以启动对重合的过敏反应食物抗原。我们将结合遗传，药理学和质谱方法严格检验该假设。如果得到确认，我们的工作对为什么过敏会增加并可能导致新的公共卫生政策和用于管理过敏性疾病的新疗法。