Previous studies demonstrated spontaneous type 2 airway inflammation with eosinophilia juvenile Scnn1b-Tg mice with muco-obstructive lung disease. Interleukin-1 receptor (IL-1R) signaling has been implicated in allergen-driven airways disease, however, its role in eosinophilic inflammation in muco-obstructive lung disease remains unknown. In this study, we examined the role of IL-1R signaling in the development of airway eosinophilia and type 2 inflammation in juvenile Scnn1b-Tg mice. We determined effects of genetic deletion of Il1r1 on eosinophil counts, transcript levels of key type 2 cytokines, markers of eosinophil activation and apoptosis, and tissue morphology in lungs of Scnn1b-Tg mice at different time points during neonatal development. Further, we measured endothelial surface expression of intercellular adhesion molecule 1 (ICAM-1), an integrin involved in eosinophil transendothelial migration, and determined effects of eosinophil depletion using an anti-IL-5 antibody on lung morphology. Lack of IL-1R reduced airway eosinophilia and structural lung damage, but did not reduce levels of type 2 cytokines and associated eosinophil activation in Scnn1b-Tg mice. Structural lung damage in Scnn1b-Tg mice was also reduced by eosinophil depletion. Lack of IL-1R was associated with reduced expression of ICAM-1 on lung endothelial cells and reduced eosinophil counts in lungs from Scnn1b-Tg mice. We conclude that IL-1R signaling is implicated in airway eosinophilia independent of type 2 cytokines in juvenile Scnn1b-Tg mice. Our data suggest that IL-1R signaling may be relevant in the pathogenesis of eosinophilic airway inflammation in muco-obstructive lung diseases, which may, in part, be mediated by ICAM-1 dependent transmigration of eosinophils into the lungs.
|Journal||American Journal of Respiratory Cell and Molecular Biology|
|Early online date||09 Sep 2019|
|Publication status||Early online date - 09 Sep 2019|
Brown, R., Paulsen, M., Schmidt, S., Schaterrny, J., Frank, A., Hirtz, S., Delaney, R., Doherty, D., Hagner, M., Taggart, C., Weldon, S., & Mall, M. A. (2019). Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease. American Journal of Respiratory Cell and Molecular Biology. https://doi.org/10.1165/rcmb.2018-0359OC