MRC-GSK Alliance: Mechanisms of interplay between allergy and viruses in asthma

MRC-GSK 联盟：哮喘中过敏和病毒之间相互作用的机制

• 批准号: G1100238/1
• 负责人: Sebastian Johnston
• 金额: $ 257.32万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1100238%2F1
• 关键词: MRC; GSK; Alliance; Mechanisms; interplay

We apply to form an Alliance between GSK and the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma to discover and develop new approaches for prevention/treatment of asthma and asthma attacks. We will integrate research in areas of major strength for the Centre with the strengths in asthma drug discovery at GSK. The overall aim is to investigate mechanisms of interplay between allergy and virus infection in development of asthma and in acute asthma attacks. The major cause of asthma attacks are human rhinovirus (RV) infections, these are also related to development of asthma when they occur in early life. We will investigate gene expression and how expression is regulated in lung cells during RV infection to identify molecules/pathways induced by RV infection that are implicated in promoting allergic responses.We will determine whether RV induction/modification of these molecules/processes are related to pre-existing allergic responses, virus load and clinical severity of asthma exacerbation. A major cause of asthma is failure of development of immunological tolerance to allergens. We have shown that tolerance can be reversed by a virus infection, but the mechanisms are unknown. We will purify lung cells from the virus-induced breakdown of tolerance model to identify genes implicated in tolerance breakdown and determine whether these are replicated in lung cells in the human.Finally we will determine whether blocking or inducing molecules implicated in virus induced worsening of allergic responses/breakdown of tolerance, determines severity of RV induced allergic airway inflammation.Accomplishment of these aims will identify targets for development of novel therapies for asthma and asthma attacks.

我们申请成立GSK与MRC & Asthma UK Centre哮喘过敏机制联盟，以发现和开发预防/治疗哮喘和哮喘发作的新方法。我们将把中心的主要优势领域的研究与GSK的哮喘药物发现优势相结合。总体目标是研究过敏和病毒感染在哮喘发展和急性哮喘发作中的相互作用机制。哮喘发作的主要原因是人鼻病毒（RV）感染，这些也与哮喘在生命早期发生时的发展有关。我们将研究RV感染过程中肺细胞中基因的表达以及表达是如何调节的，以确定RV感染诱导的分子/途径，这些分子/过程与促进过敏反应有关，我们将确定RV诱导/修饰这些分子/过程是否与预先存在的过敏反应、病毒载量和哮喘急性发作的临床严重程度有关。哮喘的主要原因是对过敏原的免疫耐受性发展失败。我们已经证明耐受性可以被病毒感染逆转，但机制尚不清楚。我们将从病毒诱导的耐受性破坏模型中纯化肺细胞，以鉴定与耐受性破坏有关的基因，并确定这些基因是否在人类肺细胞中复制。最后，我们将确定阻断或诱导与病毒诱导的过敏反应恶化/耐受性破坏有关的分子，确定RV诱导的过敏性气道炎症的严重程度。这些目标的实现将为开发哮喘和哮喘发作的新疗法确定靶点。