Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease

• Published in: American journal of respiratory cell and molecular biology Vol. 62; no. 3; pp. 300 - 309
• Main Authors: Brown, Ryan, Paulsen, Michelle, Schmidt, Simone, Schatterny, Jolanthe, Frank, Angela, Hirtz, Stephanie, Delaney, Rebecca, Doherty, Declan, Hagner, Matthias, Taggart, Cliff, Weldon, Sinéad, Mall, Marcus A
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-03-2020
• Subjects: Airway management; Chronic obstructive pulmonary disease; Cytokines; Eosinophilia; Intercellular adhesion molecule 1; Interleukin 1; Interleukin 1 receptors; Leukocytes (eosinophilic); Lung diseases; Obstructive lung disease; Respiratory tract; Respiratory tract diseases; Rodents; Sodium channels; migration; eosinophil; type 2 inflammation; IL-1
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2018-0359OC

Previous studies demonstrated spontaneous type 2 airway inflammation with eosinophilia in juvenile
(sodium channel, non-voltage-gated 1, β-subunit)-transgenic (
-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
-Tg mice. We determined effects of genetic deletion of
(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
-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
-Tg mice. Structural lung damage in
-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
-Tg mice. We conclude that IL-1R signaling is implicated in airway eosinophilia independent of type 2 cytokines in juvenile
-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.