| First Author | Brown R | Year | 2020 |
| Journal | Am J Respir Cell Mol Biol | Volume | 62 |
| Issue | 3 | Pages | 300-309 |
| PubMed ID | 31499011 | Mgi Jnum | J:302723 |
| Mgi Id | MGI:6508632 | Doi | 10.1165/rcmb.2018-0359OC |
| Citation | Brown R, et al. (2020) Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease. Am J Respir Cell Mol Biol 62(3):300-309 |
| abstractText | Previous studies demonstrated spontaneous type 2 airway inflammation with eosinophilia in juvenile Scnn1b (sodium channel, non-voltage-gated 1, beta-subunit)-transgenic (Scnn1b-Tg) mice with muco-obstructive lung disease. IL-1 receptor (IL-1R) signaling has been implicated in allergen-driven airway 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 (IL-1 receptor type I) 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. Furthermore, 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 it did not reduce concentrations 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 be mediated in part by ICAM-1-dependent transmigration of eosinophils into the lungs. |
