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

• 批准号: 10615112
• 负责人: Andrew Wang
• 金额: $ 57.47万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 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/10615112
• 关键词: Acetaminophen; Adjuvant; Affect; Allergic; Allergic Disease; American; Analgesic and Antipyretic; Analgesics; Antigen Presentation; Antigens; Cell Nucleus; Cells; Chemical Structure; Chemicals; Child; Cholera Toxin; Collaborations; 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; Predisposition; Prevalence; Process; Production; Property; Public Health; Role; Severities; Signal Transduction; Source; Specificity; Testing; Time; Work; Xenobiotics; adduct; allergic response; dosage; drug action; food antigen; food consumption; gut microbiome; intestinal epithelium; man; microbiota; novel; novel therapeutics; nuclear factor-erythroid 2; oral tolerance; pharmacologic; receptor; sensor; urban setting

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.

项目总结