The Effect of IL-17A on Dendritic Cells

ii Asthma is a chronic inflammatory disorder of the airways classically thought to result from an excessive Th2-dominated immune response to inhaled environmental antigens such as house dust mite (HDM). Recently though, the observation that individuals with severe asthma express high levels of IL-17A and IL-17F suggests that Th17 cytokines may play a role in more severe disease. In support of this, we have found that A/J mice, which develop severe AHR, mount a mixed Th2/Th17 response following HDM inhalation, while C3H/HeJ mice, which develop mild AHR, mount an exclusively Th2-biased immune response. Supporting a role for IL-17A, blockade of IL-17A in A/J mice diminished AHR, while exposure of C3H/HeJ to HDM+IL-17A exacerbated disease. In preliminary studies that form the basis of this thesis, we found that IL-17A plays different roles at different phases of the allergic response. Specifically, if present at challenge, IL-17A enhances IL-13 driven signaling while the presence of IL-17A at allergen sensitization regulates the number of Tregs present i