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.

项目概要 自 1960 年以来，由于未知原因，食物过敏呈指数级增长。我们假设 广泛引入现代环境的现代外源物质可能会产生过敏反应 佐剂会破坏口服耐受并引起过敏。该提案将探讨某些非类固醇抗氧化剂如何 炎症药物（NSAID）足以引起口服过敏。该提案将测试总体 假设佐剂 NSAID 是核因子红细胞 2 相关异生传感器的激活剂 因子 2 (NRF2)，位于肠上皮细胞中，释放 IL33 以启动对同时发生的过敏反应 食物抗原。我们将结合遗传、药理学和质谱方法来 严格检验这个假设。如果得到证实，我们的工作将对过敏增加的原因产生重大影响 并可能导致新的公共卫生政策和治疗过敏性疾病的新疗法。

项目成果

Small-molecule CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow via the endocrine stress response.

小分子 CBP/p300 组蛋白乙酰转移酶抑制通过内分泌应激反应动员骨髓中的白细胞。

• DOI: 10.1016/j.immuni.2024.01.005
• 发表时间: 2024-01-01
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Nikolai P Jaschke;Dorit Breining;Maura Hofmann;Sophie Pählig;U. Baschant;Reinhard Oertel;Sofia Traikov
• 通讯作者: Sofia Traikov