Epithelial control of responses to allergen challenge and viral exacerbation

Project SummaryIt is well known that infection by respiratory viruses (e.g., RSV or RV) can exacerbate responses in individualswho are allergic asthmatics. It is our hypothesis that the airway epithelium is the central coordinator ofresponses 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 fromasthmatics respond in a different manner to infection than AECs from healthy subjects. These differences aremanifested during infection in several ways, including changes in the expression and deposition of extracellular matrix components and qualitative and quantitative differences in the expression of cytokines andchemokines. This altered response in asthmatic AEC leads to changes in both innate and adaptive responsesduring infection, with increased infiltration of the airways with leukocytes. The primary goal of this Program isto identify and characterize these changes in asthmatic AECs, and determine their effects on the innate andadaptive immune response. With this goal in mind, we will (1) Determine the role of the epithelium inregulating ECM and leukocyte adhesion in viral-triggered asthma; (2) Determine the regulation of theInnate Immune response by the epithelium in asthma; (3) Determine the role of the epithelium inregulating T cell responses in asthma.