Grant: Operating Grant

The prevalence, morbidity and mortality of asthma have increased dramatically despite improved understanding of the disease. One important recent finding is that the newly identified inflammatory cells, so-called Th17 cells, may contribute to pathogenesis in asthma. Th17 cells produce large amounts of the inflammatory mediator, interleukin-17 (IL-17), which regulates recruitment of other cells to sites of inflammation. Data from human asthmatics suggest that Th17 cells and their protein products may play a particularly important role in more severe, steroid-resistant forms of asthma. However, the mechanisms by which these cells contribute to airway dysfunction are not understood. One of our main goals with this project is to take advantage of rodent models to better understand how Th17 cells and their cytokine product, IL-17, contribute to allergic airways disease. We will exploit models we have developed in which we can control the timing of delivery to the airways of well-defined populations of asthma-inducing inflammatory cells. We will either remove IL-17 or, using unique methodologies developed in my laboratory, overproduce IL-17 in the airways of animals with experimentally induced allergic airways disease. With these techniques, we will define the contribution of Th17 cells and IL-17 to the functional and structural changes in allergic airways, in both acute and chronic asthma models. We will also assess how Th17 cells and IL-17 affect the response to steroid treatment. Finally, we have developed a new system to investigate how IL-17 interacts with another important mediator of allergic airways disease, IL-13. Using these novel methodologies, we are uniquely placed to better understand how Th17 cells and IL-17 regulate allergic airways disease.