Epithelial regulation of ECM and leukocyte adhesion in viral-triggered asthma

项目摘要 众所周知，感染呼吸道病毒(如呼吸道合胞病毒或轮状病毒)会加剧个体的反应 他们都是过敏性哮喘患者。我们的假设是，呼吸道上皮是 对呼吸道病毒感染和过敏原的反应。呼吸道上皮细胞的内在差异 健康人和哮喘患者的血管内皮细胞(AEC)在这种加重的反应中起着重要作用。AECS发件人 哮喘患者对感染的反应方式与健康人的血管内皮细胞不同。这些区别是 在感染过程中表现为几种方式，包括Extra的表达和沉积的变化 细胞基质成分与细胞因子和细胞因子表达的质与量差异 趋化因子。哮喘AEC中这种改变的反应导致先天反应和适应性反应的改变 在感染期间，随着白细胞在呼吸道的渗透增加。该计划的主要目标是 鉴定和表征哮喘AECs的这些变化，并确定它们对先天和 适应性免疫反应。考虑到这一目标，我们将(1)确定上皮在 调节病毒触发的哮喘中的ECM和白细胞黏附；(2)确定 哮喘中上皮细胞的先天免疫反应；(3)上皮细胞在哮喘发病中的作用 调节哮喘患者的T细胞反应。

Project Summary It is well known that infection by respiratory viruses (e.g., RSV or RV) can exacerbate responses in individuals who are allergic asthmatics. It is our hypothesis that the airway epithelium is the central coordinator of responses to respiratory virus infection, as well as to allergens. Intrinsic differences in airway epithelial cells (AEC) in healthy and asthmatic individuals play an important role in this exacerbated response. AECs from asthmatics respond in a different manner to infection than AECs from healthy subjects. These differences are manifested during infection in several ways, including changes in the expression and deposition of extra cellular matrix components and qualitative and quantitative differences in the expression of cytokines and chemokines. This altered response in asthmatic AEC leads to changes in both innate and adaptive responses during infection, with increased infiltration of the airways with leukocytes. The primary goal of this Program is to identify and characterize these changes in asthmatic AECs, and determine their effects on the innate and adaptive immune response. With this goal in mind, we will (1) Determine the role of the epithelium in regulating ECM and leukocyte adhesion in viral-triggered asthma; (2) Determine the regulation of the Innate Immune response by the epithelium in asthma; (3) Determine the role of the epithelium in regulating T cell responses in asthma.