Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze
(2020) In Allergy: European Journal of Allergy and Clinical Immunology 75(12). p.3195-3207- Abstract
Background: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. Methods: Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor... (More)
Background: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. Methods: Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL-33 and receptor ST2 were investigated in bronchial biopsies. Results: PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti-viral and pro-inflammatory cytokines (IFN-γ, IL-6 and IL-13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound-healing was also impaired in PSW compared to controls at baseline and following IL-33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. Conclusions: Despite increased anti-viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.
(Less)
- author
- Andersson, Cecilia K. LU ; Iwasaki, Jua ; Cook, James ; Robinson, Polly ; Nagakumar, Prasad ; Mogren, Sofia LU ; Fleming, Louise ; Bush, Andrew ; Saglani, Sejal and Lloyd, Clare M.
- organization
- publishing date
- 2020-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- epithelium, paediatric asthma, RSV, severe therapy-resistant asthma, wheeze
- in
- Allergy: European Journal of Allergy and Clinical Immunology
- volume
- 75
- issue
- 12
- pages
- 13 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:32578219
- scopus:85087875593
- ISSN
- 0105-4538
- DOI
- 10.1111/all.14466
- language
- English
- LU publication?
- yes
- id
- c994af78-e253-42b2-b253-818eef8116a1
- date added to LUP
- 2020-07-30 11:33:04
- date last changed
- 2024-05-30 20:08:14
@article{c994af78-e253-42b2-b253-818eef8116a1,
abstract = {{<p>Background: Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. Methods: Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL-33 and receptor ST2 were investigated in bronchial biopsies. Results: PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti-viral and pro-inflammatory cytokines (IFN-γ, IL-6 and IL-13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound-healing was also impaired in PSW compared to controls at baseline and following IL-33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. Conclusions: Despite increased anti-viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.</p>}},
author = {{Andersson, Cecilia K. and Iwasaki, Jua and Cook, James and Robinson, Polly and Nagakumar, Prasad and Mogren, Sofia and Fleming, Louise and Bush, Andrew and Saglani, Sejal and Lloyd, Clare M.}},
issn = {{0105-4538}},
keywords = {{epithelium; paediatric asthma; RSV; severe therapy-resistant asthma; wheeze}},
language = {{eng}},
number = {{12}},
pages = {{3195--3207}},
publisher = {{Wiley-Blackwell}},
series = {{Allergy: European Journal of Allergy and Clinical Immunology}},
title = {{Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze}},
url = {{http://dx.doi.org/10.1111/all.14466}},
doi = {{10.1111/all.14466}},
volume = {{75}},
year = {{2020}},
}