IL-33 Signalling Contributes to Diesel Exhaust Particles (DEP)-Induced Asthma Exacerbations and Recall Responses.
Saturday, March 4, 2017: 1:45 PM
Room B314 (Georgia World Congress Center, Building B)
Eric B. Brandt, PhD FAAAAI, , ,
Rationale: Exposure to traffic pollution, notably diesel exhaust particles (DEP), increases risk for asthma and asthma exacerbations. The contribution of IL-33, an alarmin generated by stressed lung epithelial cells, remains poorly understood. Our main objective is to determine the importance of IL-33 signalling through its receptor ST2 in DEP-induced asthma exacerbations in a well characterized murine model. 

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.