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.
Asthma is the most common chronic lung disease among adults and children, affecting nearly 26 million people in the U.S, including 10 million children. Current standard of care treatments for persistent asthma, including inhaled ?-agonists and inhaled corticosteroids, are effective at improving symptoms and decreasing the frequency and severity of exacerbations, however, they do not alter the natural course of the disease. Therefore, newer treatment strategies that target the mechanisms that drive airway remodeling and chronic airway inflammation are needed. The studies in this Center are designed to determine the role of the airway epithelium in virus-induced exacerbation to gain insights into new pathways that may yield new therapeutic targets.
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