Role of the indoor exposome in peanut allergy development

摘要 越来越多的证据表明，早期的环境暴露是导致 包括食物过敏在内的过敏性疾病日益流行。食物过敏率，尤其是 对于花生，在过去的几十年里，在工业化国家急剧增加， 这表明环境因素正在推动疫情的蔓延。最近的研究表明，吸入性 或者在家中皮肤接触花生可能是花生过敏的一个风险因素。在……里面 除了食物抗原，室内暴露体还包括免疫刺激剂，如 微生物产品和空气污染物，可作为佐剂并促进过敏 对抗原敏感。接触环境佐剂是否会影响花生过敏 事态发展尚不明朗。我们已经开发出一种新的模拟吸入性的小鼠模型 在家中接触环境花生米。我们已经发现，联合暴露于吸入 花生和室内粉尘，其中含有儿童接触到的环境助剂， 诱导小鼠过敏反应和花生过敏反应的发生。此外，我们有 发现共同暴露在吸入花生和空气污染物中，包括柴油废气颗粒物和 颗粒物，在我们的动物模型中也会引起花生过敏。在这项提案中，我们将 确定暴露于室内粉尘中的环境佐剂是否与花生有关 婴儿的致敏作用，还研究了环境佐剂 (如室内粉尘、空气污染物)会促进花生过敏的发展。在目标1中，我们将使用 呼吸道致敏动物模型及原代人支气管上皮细胞培养体系 比较从花生家中采集的室内粉尘样本的佐剂活性- 致敏和非致敏婴儿，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 室内粉尘对花生的呼吸道致敏所需的途径。在《目标3》中，我们将 吸入空气污染物促进花生过敏的免疫学机制研究 我们的动物模型的发展。这些研究将极大地扩展我们对 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。

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.