{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:27:51Z","timestamp":1770834471543,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,3,1]],"date-time":"2020-03-01T00:00:00Z","timestamp":1583020800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Previous studies demonstrated spontaneous type 2 airway inflammation with eosinophilia in juvenile Scnn1b (sodium channel, non\u2013voltage-gated 1, \u03b2-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\u2013IL-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\u2013dependent transmigration of eosinophils into the lungs.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0359oc","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T17:20:32Z","timestamp":1568049632000},"page":"300-309","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":7,"title":["Lack of IL-1 Receptor Signaling Reduces Spontaneous Airway Eosinophilia in Juvenile Mice with Muco-Obstructive Lung Disease"],"prefix":"10.1093","volume":"62","author":[{"given":"Ryan","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Translational Pulmonology, Translational Lung Research Centre Heidelberg, German Center for Lung Research, University of Heidelberg, Heidelberg, 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