The research in the Lewkowich Lab focuses on identifying the mechanisms through which IL-17A can enhance the severity of allergic asthma. The pathogenesis of allergic asthma is associated with the development of an inappropriate Th2 dominated immune response to normally innocuous environmental allergens (i.e. pet dander, house dust mites, pollens). In most individuals, therapeutic interventions effectively manage symptoms, but in those with the most severe disease, common therapies are not effective. As a result, individuals with severe asthma are more prone to serious exacerbations of disease that can result in hospitalization or even death.
Making use of primary, asthma relevant tissues from animals, and pediatric donors, we have identified a role for the Th17 cytokine IL-17A in driving the development of severe allergic asthma.
Specifically the lab has found that mice strains that develop more severe asthma develop a mixed Th2/Th17 immune response after exposure to the aeroallergen house dust mite (HDM), whereas those that develop mild asthma have a Th2-dominated immune response. Blockade of IL-17A in mice with severe asthma reduces the severity of disease, while administration of IL-17A to mice with mild asthma promotes the development of severe asthma. Moreover, while IL-17A administration to the lungs of mice is unable to induce any symptoms of allergic asthma, administration of IL-17A in the presence of the Th2 effector cytokine IL-13 induces more severe symptoms than administration of IL-13 alone. This suggests that IL-17A regulates disease severity by enhancing the activity of IL-13.