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Tumor necrosis factor family member LIGHT acts with IL ‐1β and TGF ‐β to promote airway remodeling during rhinovirus infection
Author(s) -
Mehta A. K.,
Doherty T.,
Broide D.,
Croft M.
Publication year - 2018
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13390
Subject(s) - rhinovirus , immunology , medicine , allergen , fibrosis , house dust mite , asthma , lung , airway , tumor necrosis factor alpha , cystic fibrosis , inflammation , transforming growth factor , allergy , pathology , virus , surgery
Background Rhinovirus ( RV ) can exacerbate allergen‐driven asthma. However, it has been suggested that serial infections with RV may also lead to asthma‐like features in childhood without prior allergen exposure. Aim We sought to test the effects of RV infection in the absence of allergen challenge on lung tissue remodeling and to understand whether RV induced factors in common with allergen that promote remodeling. Methods We infected C57 BL /6 mice multiple times with RV in the absence or presence of allergen to assess airway remodeling. We used knockout mice and blocking reagents to determine the participation of LIGHT ( TNFSF 14), as well as IL ‐1β and TGF ‐β, each previously shown to contribute to lung remodeling driven by allergen. Results Recurrent RV infection without allergen challenge induced an increase in peribronchial smooth muscle mass and subepithelial fibrosis. Rhinovirus ( RV ) induced LIGHT expression in mouse lungs after infection, and alveolar epithelial cells and neutrophils were found to be potential sources of LIGHT . Accordingly, LIGHT ‐deficient mice, or mice where LIGHT was neutralized, displayed reduced smooth muscle mass and lung fibrosis. Recurrent RV infection also exacerbated the airway remodeling response to house dust mite allergen, and this was significantly reduced in LIGHT ‐deficient mice. Furthermore, neutralizing IL ‐1β or TGF ‐β also limited subepithelial fibrosis and/or smooth muscle thickness induced by RV . Conclusion Rhinovirus can promote airway remodeling in the absence of allergen through upregulating common factors that also contribute to allergen‐associated airway remodeling.