Methods: ST2 deficient and Balb/c control mice were exposed nine times over a 3-week period to house dust mite (HDM) ± DEP. Seven weeks later, some mice received a single HDM challenge to assess memory responses. Airway hyper-responsiveness (AHR), BALF inflammation and lung T-cell subsets were assessed after primary and recall responses.
Results: DEP co-exposure with HDM resulted in a mixed Th2/Th17 response in the lungs of exposed mice. After 7 weeks of rest, a single exposure to HDM induced AHR more strongly in mice previously exposed to both HDM and DEP versus HDM alone. AHR was significantly lower in ST2 deficient mice compared to wild type controls after both the primary HDM±DEP exposures and the HDM recall. Interestingly, Th17 rather than Th2 lung cell levels were primarly decreased in ST2 deficient mice, most notably IL5/IL13/IL17A producing CD4+ T-cells.
Conclusions: IL-33 contributes to DEP-induced asthma exacerbations and the accumulation of pathogenic Th2/Th17 cells in the lungs of HDM and DEP co-exposed mice.