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

Ryan Brown, Michelle Paulsen, Simone Schmidt, Jolanthe Schaterrny, Angela Frank, Stephanie Hirtz, Rebecca Delaney, Declan Doherty, Matthias Hagner, Cliff Taggart, Sinead Weldon, Marcus A Mall

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Early online date09 Sep 2019
DOIs
Publication statusEarly online date - 09 Sep 2019

Fingerprint

Obstructive Lung Diseases
Pulmonary diseases
Interleukin-1 Receptors
Eosinophilia
Eosinophils
Lung
Intercellular Adhesion Molecule-1
Cytokines
Inflammation
Chemical activation
Interleukin-5
Endothelial cells
Transendothelial and Transepithelial Migration
Integrins
Allergens
Tissue
Apoptosis
Endothelial Cells
Antibodies

Cite this

@article{d76388728f024babb626f955b4875e7a,
title = "Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease",
abstract = "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.",
author = "Ryan Brown and Michelle Paulsen and Simone Schmidt and Jolanthe Schaterrny and Angela Frank and Stephanie Hirtz and Rebecca Delaney and Declan Doherty and Matthias Hagner and Cliff Taggart and Sinead Weldon and Mall, {Marcus A}",
year = "2019",
month = "9",
day = "9",
doi = "10.1165/rcmb.2018-0359OC",
language = "English",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",

}

Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease. / Brown, Ryan; Paulsen, Michelle; Schmidt, Simone; Schaterrny, Jolanthe ; Frank, Angela; Hirtz, Stephanie; Delaney, Rebecca; Doherty, Declan; Hagner, Matthias; Taggart, Cliff; Weldon, Sinead; Mall, Marcus A.

In: American Journal of Respiratory Cell and Molecular Biology, 09.09.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease

AU - Brown, Ryan

AU - Paulsen, Michelle

AU - Schmidt, Simone

AU - Schaterrny, Jolanthe

AU - Frank, Angela

AU - Hirtz, Stephanie

AU - Delaney, Rebecca

AU - Doherty, Declan

AU - Hagner, Matthias

AU - Taggart, Cliff

AU - Weldon, Sinead

AU - Mall, Marcus A

PY - 2019/9/9

Y1 - 2019/9/9

N2 - 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.

AB - 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.

U2 - 10.1165/rcmb.2018-0359OC

DO - 10.1165/rcmb.2018-0359OC

M3 - Article

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

ER -