Role of the indoor exposome in peanut allergy development

室内暴露组在花生过敏发展中的作用

• 批准号: 10359436
• 负责人: Timothy Moran
• 金额: $ 54.42万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-22 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359436
• 关键词: Adjuvant; Agonist; Air Pollutants; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Anaphylaxis; Animal Model; Antigens; Automobile Driving; B-Lymphocytes; Birth; Cell Culture System; Cell Line; Child; Childhood; Cohort Studies; Cutaneous; Data; Dendritic Cells; Developed Countries; Development; Diesel Exhaust; Dust; Environmental Exposure; Environmental Risk Factor; Epidemic; Epithelial Cells; Exposure to; Food; Food Hypersensitivity; Future; Helper-Inducer T-Lymphocyte; Home; Human; IgE; Immune signaling; Immunologics; Infant; Inhalation; Inhalation Exposure; Interleukin-1; Life; Ligands; Lung; Measures; Mediating; Modeling; Mucous Membrane; Mus; National Institute of Environmental Health Sciences; Particulate Matter; Prevalence; Production; Receptor Signaling; Reporter; Reporting; Research; Research Priority; Respiratory System; Risk; Risk Factors; Role; Sampling; Signal Pathway; Signal Transduction; Signaling Molecule; Skin; Source; Strategic Planning; T-Lymphocyte; Toll-like receptors; airway epithelium; biomass smoke; bronchial epithelium; career; coarse particles; cytokine; environmental agent; environmental intervention; fine particles; food antigen; indoor dust; lymph nodes; microbial; migration; mouse model; novel; particle; prevent; programs; remediation; sensitizing antigen

ABSTRACT There is growing evidence that early-life environmental exposures are contributing to the increasing prevalence of allergic diseases including food allergy. Food allergy rates, particularly for peanut, have increased dramatically in industrialized countries over the last few decades, suggesting environmental factors are driving the epidemic. Recent studies show that inhalational or cutaneous exposure to peanut within the home may be a risk factor for peanut allergy. In addition to food antigens, the indoor exposome also includes immunostimulatory agents, such as microbial products and air pollutants, which can act as adjuvants and promote allergic sensitization to antigens. Whether exposure to environmental adjuvants influences peanut allergy development is unclear. We have developed a novel mouse model that mimics inhalational exposure to environmental peanut within the home. We have found that co-exposure to inhaled peanut and indoor dust, which contains environmental adjuvants to which children are exposed, induced allergic sensitization and the development of peanut allergy in mice. Moreover, we have found that co-exposure to inhaled peanut and air pollutants, including diesel exhaust particles and particulate matter, also induced peanut allergy in our animal model. In this proposal, we will determine if exposure to environmental adjuvants in indoor dust is associated with peanut sensitization in infants, and also investigate the mechanisms by which environmental adjuvants (e.g., indoor dust, air pollutants) promote peanut allergy development. In Aim 1, we will use an airway sensitization animal model and primary human bronchial epithelial cell culture system to compare the adjuvant activity of indoor dust samples collected from the homes of peanut- sensitized and nonsensitized infants, and determine if adjuvant activity is associated with peanut sensitization status. In Aim 2, we will use animal models to define the innate immune signaling pathways required for indoor dust-mediated airway sensitization to peanut. In Aim 3, we will investigate the immunological mechanisms by which inhaled air pollutants promote peanut allergy development in our animal model. These studies will greatly expand our understanding of how the indoor exposome influences food allergy development and help direct future environmental interventions aimed at preventing peanut allergy in children.

抽象的 越来越多的证据表明，生命早期的环境暴露正在导致 包括食物过敏在内的过敏性疾病的患病率不断增加。食物过敏率，特别是 过去几十年来，工业化国家的花生数量急剧增加， 表明环境因素正在推动这一流行病。最近的研究表明，吸入 或在家中皮肤接触花生可能是花生过敏的危险因素。在 除了食物抗原外，室内暴露组还包括免疫刺激剂，例如 微生物产物和空气污染物，可以作为佐剂并促进过敏 对抗原的敏化。接触环境助剂是否影响花生过敏 发展尚不清楚。我们开发了一种模仿吸入的新型小鼠模型 在家中接触环境花生。我们发现共同暴露于吸入 花生和室内灰尘，其中含有儿童接触的环境助剂， 诱导小鼠过敏致敏和花生过敏的发生。此外，我们还有 发现同时吸入花生和空气污染物，包括柴油机尾气颗粒和 颗粒物也在我们的动物模型中诱发花生过敏。在本提案中，我们将 确定接触室内灰尘中的环境助剂是否与花生有关 婴儿致敏，并研究环境佐剂的机制 （例如室内灰尘、空气污染物）会促进花生过敏。在目标 1 中，我们将使用 气道致敏动物模型及原代人支气管上皮细胞培养系统 比较从花生家庭收集的室内灰尘样品的辅助活性 过敏和非过敏婴儿，并确定佐剂活性是否与花生有关 敏化状态。在目标 2 中，我们将使用动物模型来定义先天免疫信号 室内灰尘介导的气道对花生过敏所需的途径。在目标 3 中，我们将 研究吸入空气污染物促进花生过敏的免疫机制 我们的动物模型的发展。这些研究将极大地扩展我们对如何 室内暴露影响食物过敏的发展并有助于指导未来的环境 旨在预防儿童花生过敏的干预措施。