IL-33 promotes airway remodeling in pediatric patients with severe steroid-resistant asthma
Open accessAbstract
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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SAA/IL-33 play a role in the pathology of steroid-resistant lung inflammation.
“It has been shown that SAA/IL-33 play a role in the pathology of steroid-resistant lung inflammation [6,15].”
IL-33 is implicated as a steroid-resistant mediator that promotes airway remodeling in patients with severe therapy-resistant asthma.
“Moreover, IL-33 has been implicated as a steroid-resistant mediator that promotes airway remodeling in patients with severe therapy-resistant asthma [15].”
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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
- 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)
- 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 · 2012: 1
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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 › Physiology › 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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