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

 描述(申请人提供)：过敏性疾病在美国和世界范围内影响着越来越多的人。在这些疾病中，过敏性哮喘因其高发病率和经济负担而特别令人担忧。虽然医学在治疗哮喘症状方面取得了重大进展，但真正治愈这种疾病的方法仍然遥不可及。许多寻求治疗哮喘的研究人员都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)做出不适当的反应，如屋尘螨(HDM)。正常人在遇到这种过敏原时不会经历免疫反应，据说对过敏原有耐受性。然而，哮喘患者缺乏这种耐受性，并经历了破坏性的炎症反应。了解耐受性是如何形成的，以及为什么哮喘患者缺乏耐受性，对于开发真正的治疗方法至关重要。免疫系统拥有有助于控制免疫反应的调节元素。以前的工作表明，其中之一的调节性T细胞(Treg)在建立耐受性方面起着关键作用 对过敏原过敏。然而，在健康人中产生Tregs并预防哮喘的机制仍不清楚。对免疫系统可能产生影响的一个因素是微生物群落，也就是生活在我们每个人身上和体内的微生物群落。在过去的十年里，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Tregs。许多研究表明，微生物组的丢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具有关键影响。这一建议假设微生物群通过促进Treg的形成来促进对屋尘螨(HDM)等过敏原的耐受性。这项建议的总体目标是确定接触HDM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：拟议目标的完成可能会揭示基于微生物组的疗法的新机会，这些疗法可以为哮喘提供根治疗法。

 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.