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Impaired airway epi...
Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze
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- Andersson, Cecilia K. (author)
- Lund University,Lunds universitet,Respiratorisk cellbiologi,Forskargrupper vid Lunds universitet,Respiratory Cell Biology,Lund University Research Groups,Imperial College London
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- Iwasaki, Jua (author)
- Imperial College London
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- Cook, James (author)
- Harefield Hospital,Imperial College London
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- Robinson, Polly (author)
- Harefield Hospital,Imperial College London
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- Nagakumar, Prasad (author)
- Harefield Hospital,Imperial College London
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- Mogren, Sofia (author)
- Lund University,Lunds universitet,Respiratorisk cellbiologi,Forskargrupper vid Lunds universitet,Respiratory Cell Biology,Lund University Research Groups
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- Fleming, Louise (author)
- Harefield Hospital
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- Bush, Andrew (author)
- Harefield Hospital
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- Saglani, Sejal (author)
- Imperial College London,Harefield Hospital
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- Lloyd, Clare M. (author)
- Imperial College London
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(creator_code:org_t)
- 2020-07-15
- 2020
- English 13 s.
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In: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 75:12, s. 3195-3207
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Keyword
- epithelium
- paediatric asthma
- RSV
- severe therapy-resistant asthma
- wheeze
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Andersson, Cecil ...
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Iwasaki, Jua
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Cook, James
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Robinson, Polly
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Nagakumar, Prasa ...
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Mogren, Sofia
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show more...
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Fleming, Louise
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Bush, Andrew
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Saglani, Sejal
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Lloyd, Clare M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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Allergy: Europea ...
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Allergy
- By the university
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Lund University