Role of the Microbiome in Regulating House Dust Mite-Induced Asthma

 描述（由申请人提供）：过敏性疾病影响越来越多的人在美国和世界各地。在这些疾病中，过敏性哮喘由于其高发病率和经济负担而特别令人关注。虽然医学科学在治疗哮喘症状方面取得了深刻的进展，但真正治愈这种疾病的方法仍然难以捉摸。许多寻求治疗哮喘的研究人员将注意力集中在免疫系统上。在哮喘中，免疫系统对环境中常见的无害产品（“过敏原”）（如屋尘螨（HDM））做出不适当的反应。正常个体在遇到这种过敏原时不会经历免疫应答，并且据说对过敏原是耐受的。然而，哮喘患者缺乏这种耐受性，并经历破坏性炎症反应。了解耐受性如何发展以及为什么哮喘缺乏耐受性对于开发真正的治疗至关重要。免疫系统具有帮助控制免疫应答的调节元件。以前的研究表明，其中之一，调节性T细胞（Treg），在建立耐受性中起着关键作用 过敏原。然而，TdR产生和预防健康人哮喘的机制仍然未知。对免疫系统的一个可能影响是微生物组，即生活在我们每个人身上和体内的微生物群落。在过去的十年中，研究人员发现微生物组可以对免疫系统产生调节作用，包括诱导THBG。许多研究表明，微生物组的丧失或破坏会促进过敏和哮喘;因此，微生物组可能对耐受性的发展产生关键影响。该提案假设微生物组通过促进Treg形成来促进对过敏原如屋尘螨（HDM）的耐受性。该提案的总体目标是确定HDM暴露对微生物组的影响以及微生物组与过敏性疾病和耐受性的关系。总体影响：完成拟议的目标可能会为基于微生物组的疗法提供新的机会，这些疗法可以为哮喘提供治愈性治疗。

 DESCRIPTION (provided by applicant): Allergic diseases affect an increasing number of people in the United States and worldwide. Among these diseases, allergic asthma is particularly concerning because of its high morbidity and financial burden. While medical science has made profound advances in the treatment of asthma symptoms, a true cure for the disease remains elusive. Many researchers seeking a cure for asthma have focused their attention on the immune system. In asthma, the immune system reacts inappropriately to common, harmless products ("allergens") in the environment, such as house dust mite (HDM). Normal individuals do not experience an immune response when encountering such allergens and are said to be tolerant to the allergen. However, asthma suffers lack this tolerance and experience a damaging inflammatory response. Understanding how tolerance develops and why it is lacking in asthma is critical for development of a true cure. The immune system possesses regulatory elements that help control immune responses. Previous work has shown that one of these, the regulatory T cell (Treg), plays a key role in the establishment of tolerance to allergens. However, the mechanisms by which Tregs are generated and prevent asthma in healthy people remains unknown. One possible influence on the immune system is the microbiome, the community of microorganisms that live on and within each of us. Over the past decade, researchers have discovered that the microbiome can exert regulatory effects on the immune system, including induction of Tregs. Many studies have shown that loss or disruption of the microbiome promotes allergy and asthma; thus, the microbiome may have a key influence on tolerance development. This proposal hypothesizes that the microbiome promotes tolerance to allergens like house dust mite (HDM) through promotion of Treg formation. The overall goal of this proposal is to determine the effect of HDM exposure on the microbiome and the relationship of the microbiome to allergic disease and tolerance. Overall Impact: Completion of the proposed aims may reveal new opportunities for microbiome-based therapies that could provide curative treatments for asthma.