Systemic and intercellular gene networks underlying RV-induced airways disease

呼吸道病毒感染会引发儿童喘息性疾病，并增加这些儿童患肺炎的风险 继续发展成哮喘。现在人们认识到，哮喘在儿童中并不平等。确实有 不同形式的哮喘，哮喘的风险在喘息的儿童中最高，他们也有过敏症状。它是 目前尚不清楚为什么患有喘息和过敏的儿童更容易感染呼吸道病毒 感染，更有可能发展成哮喘。然而，我们之前研究的一个重要线索是， 与病毒引起的喘息的风险和保护相关的免疫因素可以在局部找到 在呼吸道和肺部，也在血液和骨髓系统中。这表明我们最重要的是 假设决定病毒诱发喘息易感性的免疫学机制起作用 局部和全身通过肺-血-骨髓轴。在这里，我们将研究系统免疫 有或无喘息、过敏性炎症或两者兼有的儿童对病毒的反应。这项研究将 需要在病毒存在或不存在的情况下培养儿童的血源性免疫细胞。分子 将采用简档技术来表征对病毒的免疫反应 单个细胞，这些反应将在有或没有喘息的儿童组中进行比较和对比 和/或过敏性炎症。我们假设哮喘的风险是由生物平衡决定的。 控制病毒免疫反应的两种免疫因子的活性：干扰素调节因子7 和高亲和力免疫球蛋白E受体亚单位γ(FCER1G)。我们还假设一个 高度专门化的免疫细胞群称为树突状细胞，控制着IRF7和FCER1G的平衡 活动。这项研究的发现很重要，因为每13个美国人中就有1个受到哮喘的影响，而且 儿童中常见的慢性病。在美国，每年哮喘占5%以上 全科医生就诊100万人次，急诊科就诊150多万人次，出院近200,000人次 来自医院的住院治疗。此外，在美国，每天大约有11人死于哮喘 各州。了解决定哮喘风险的免疫学和分子因素将为 用于开发治疗或预防哮喘的新方法，并减轻这方面的总体负担 疾病对儿童及其家庭的影响。

Respiratory viral infections trigger wheezing illnesses in children and increase the risk that these children will go on to develop asthma. It is now recognized that asthma is not created equal among children. There are different forms of asthma, and risk for asthma is highest among wheezing children who also have allergies. It is currently not well understood why children with wheezing and allergies are more susceptible to respiratory viral infections and more likely to develop asthma. However, an important clue from our previous studies is that the immune factors that are associated with risk versus protection to virus-induced wheezing can be found locally in the airways and lung and also systematically in the blood and bone marrow. This suggested our overarching hypothesis that the immunological mechanisms that determine susceptibility to virus-induced wheezing operate both locally and systemically through a lung-blood-bone marrow axis. Here, we will study systemic immune responses to viruses in children with or without wheezing, allergic inflammation, or both. The research will entail culturing blood-derived immune cells from the children in the presence or absence of a virus. Molecular profiling technologies will be employed to characterize immune responses to the virus at the resolution of single cells, and the responses will be compared and contrasted in groups of children with or without wheezing and/or allergic inflammation. We hypothesize that risk for asthma is determined by the balance of the biological activity of two immune factors that control immune responses to viruses: Interferon regulatory factor 7 (IRF7) and the high-affinity immunoglobulin E receptor subunit gamma (FCER1G). We additionally hypothesize that a highly specialized population of immune cells called dendritic cells control the balance of IRF7 and FCER1G activity. The findings from this study are important because asthma affects 1 in 13 Americans and is the most common chronic disease among children. Each year in the United States, asthma accounts for more than 5 million GP visits, more than 1.5 million visits to the emergency department, and almost 200,000 discharges from hospital inpatient care. Moreover, approximately 11 people die from asthma every day in the United States. Understanding the immunological and molecular factors that determine asthma risk will pave the way for the development of new approaches to treat or prevent asthma and reduce the overall burden of this disease on children and their families.