Cited by 258IL-33, ST2, and ILC PathwaysAsthma and respiratory diseasesDermatology and Skin Diseases

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IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma

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Saglani, Sejal, Lui, Stephen, Ullmann, Nicola, Campbell, Gaynor A., Sherburn, Rebekah T., Mathie, Sara A., Denney, Laura, Bossley, Cara J., Oates, Timothy, Walker, Simone A., Bush, Andrew, Lloyd, Clare M.·2013·Journal of Allergy and Clinical Immunology

DOI 10.1016/j.jaci.2013.04.012PMC PMC4218948

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Abstract

Background TH2 cytokines are not responsible for the ongoing symptoms and pathology in children with severe therapy-resistant asthma (STRA). IL-33 induces airway hyperresponsiveness, but its role in airway remodeling and steroid resistance is unknown. Objective We sought to investigate the relationship between IL-33 and airway remodeling in pediatric patients with STRA. Methods IL-33 levels were quantified in neonatal mice given inhaled house dust mite (HDM), and the effect of blocking IL-13 on remodeling and IL-33 levels was assessed. HDM-induced allergic airways disease (AAD) in neonatal ST2(-/-) mice lacking the IL-33 receptor was assessed, together with collagen production after IL-33 administration. The effect of steroid therapy on IL-33 levels in patients with neonatal AAD was explored. IL-33 expression was quantified in endobronchial biopsy (EB) specimens from children with STRA and related to remodeling, and collagen production by airway fibroblasts from pediatric patients stimulated with IL-33 and budesonide was quantified. Results Blocking IL-13 after AAD was established in neonatal mice and did not reduce remodeling or IL-33 levels; airway hyperresponsiveness was only partially reduced. IL-33 promoted collagen synthesis both from asthmatic fibroblasts from pediatric patients and after intranasal administration in mice. Increased cellular expression of IL-33, but not IL-13, was associated with increased reticular basement membrane thickness in EB specimens from children with STRA, whereas remodeling was absent in HDM-exposed ST2(-/-) mice. IL-33 levels were maintained, whereas IL-13 levels were abrogated by steroid treatment in neonatal HDM-exposed mice and in EB specimens from children with STRA. Conclusion IL-33 is a relatively steroid-resistant mediator that promotes airway remodeling in patients with STRA and is an important therapeutic target.

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Saglani, 2009, Pathophysiological features of asthma develop in parallel in house dust mite exposed neonatal mice, Am J Respir Cell Mol Biol, 41, 281, 10.1165/rcmb.2008-0396OC · DOI
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Authors: Saglani, S., Lui, S., Ullmann, N., Campbell, G. A., Sherburn, R. T., Mathie, S. A., Denney, L., Bossley, C. J., Oates, T., Walker, S. A., Bush, A., & Lloyd, C. M.
Affiliations: Royal Brompton Hospital (GB)
Imperial College London (GB)
Corresponding author: Lloyd, Clare M.
ORCID: Saglani, Sejal
Ullmann, Nicola
Sherburn, Rebekah T.
Denney, Laura
Bossley, Cara J.
Bush, Andrew
Lloyd, Clare M.
Venue: Journal of Allergy and Clinical Immunology
Publisher: Elsevier BV
Published: 2013-09
Volume: 132
Issue: 3
Pages: 676-685.e13
ISSN: 0091-6749 (ISSN-L)
DOI: 10.1016/j.jaci.2013.04.012
PMC: PMC4218948
OpenAlex: W2030003617
Cited by: 258
References: 37
Citations by year: 2026: 6 · 2025: 12 · 2024: 12 · 2023: 11 · 2022: 14 · 2021: 27 · 2020: 22 · 2019: 34 · 2018: 19 · 2017: 30 · 2016: 20 · 2015: 23 · 2014: 25 · 2013: 2
FWCI: 10.20
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Allergy and Clinical Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Wellcome Trust (087618)
National Institute for Health and Care Research (NF-SI-0510-10192)
Medical Research Council (MR/J010529/1)
Topics: Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Keywords: IL-33, airway remodeling, steroid-resistant asthma, childhood asthma, IL-13, allergic airway disease, house dust mites, airway hyperresponsiveness, collagen synthesis, airway fibroblasts, budesonide, bronchial biopsy
MeSH terms: Interleukin-33, Adolescent, Animals, Animals, Newborn, Anti-Inflammatory Agents, Asthma, Child, Collagen, Drug Resistance, Female, Glucocorticoids, Humans, Interleukins, Male, Mice, Inbred BALB C, Bronchial Hyperreactivity, Mice, Knockout, Interleukin-13, Budesonide, Pyroglyphidae, Mice, Airway Remodeling

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IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma

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