Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation.

Autor: Ortiz-Zapater E; Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK.; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science King's College London, London, UK., Bagley DC; Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK., Hernandez VL; Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK., Roberts LB; School of Immunology and Microbial Sciences, King's College London, London, UK., Maguire TJA; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London, UK., Voss F; Max-Delbrück-Centrum für Molekulare Medizin in the Helmholtz Assoziation (MDC), Berlin, Germany.; DZHK Partner site Berlin, Berlin, Germany., Mertins P; Berlin Institute of Health at Charité, Universitaetsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany., Kirchner M; Berlin Institute of Health at Charité, Universitaetsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany., Peset-Martin I; Medicines Discovery Catapult, Alderley Park, Macclesfield, Cheshire, UK., Woszczek G; School of Immunology and Microbial Sciences, King's College London, London, UK., Rosenblatt J; Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK., Gotthardt M; Max-Delbrück-Centrum für Molekulare Medizin in the Helmholtz Assoziation (MDC), Berlin, Germany.; Berlin Institute of Health at Charité, Universitaetsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.; Charité Universitätsmedizin Berlin, Berlin, Germany., Santis G; Peter Gorer Department of Immunobiology, School of Immunology and Microbial Science King's College London, London, UK.; Department of Respiratory Medicine, Guy's & St Thomas NHS Trust, London, UK., Parsons M; Randall Centre for Cell & Molecular Biophysics, King's College London, London, UK. maddy.parsons@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Oct 27; Vol. 13 (1), pp. 6407. Date of Electronic Publication: 2022 Oct 27.
DOI: 10.1038/s41467-022-33882-w
Abstrakt: Airway inflammation and remodelling are important pathophysiologic features in asthma and other respiratory conditions. An intact epithelial cell layer is crucial to maintain lung homoeostasis, and this depends on intercellular adhesion, whilst damaged respiratory epithelium is the primary instigator of airway inflammation. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and facilitates immune cell transepithelial migration. However, the contribution of CAR to lung inflammation remains unclear. Here we investigate the mechanistic contribution of CAR in mediating responses to the common aeroallergen, House Dust Mite (HDM). We demonstrate that administration of HDM in mice lacking CAR in the respiratory epithelium leads to loss of peri-bronchial inflammatory cell infiltration, fewer goblet-cells and decreased pro-inflammatory cytokine release. In vitro analysis in human lung epithelial cells confirms that loss of CAR leads to reduced HDM-dependent inflammatory cytokine release and neutrophil migration. Epithelial CAR depletion also promoted smooth muscle cell proliferation mediated by GSK3β and TGF-β, basal matrix production and airway hyperresponsiveness. Our data demonstrate that CAR coordinates lung inflammation through a dual function in leucocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in inflammatory lung diseases.
(© 2022. The Author(s).)
Databáze: MEDLINE
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