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

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

dc.contributor.author	Ortiz Zapater, Elena
dc.contributor.author	Llopis Hernandez, Virginia
dc.contributor.author	Peset Martin, Isabel
dc.contributor.author	Roberts, Luke B.
dc.contributor.author	Maguire, Thomas J.A.
dc.contributor.author	Voss, Felizia
dc.contributor.author	Mertins, Philipp
dc.contributor.author	Kirchner, Marieluise
dc.contributor.author	Bagley, Dustin C.
dc.contributor.author	Woszczek, Grzegorz
dc.contributor.author	Rosenblatt, Jody
dc.contributor.author	Gotthardt, Michael
dc.contributor.author	Santis, George
dc.contributor.author	Parsons, Maddy
dc.date.accessioned	2023-05-30T11:27:43Z
dc.date.available	2023-05-30T11:27:43Z
dc.date.issued	2022
dc.identifier.citation	Ortiz Zapater, Elena Llopis Hernandez, Virginia Peset Martin, Isabel Roberts, Luke B. Maguire, Thomas J.A. Voss, Felizia Mertins, Philipp Kirchner, Marieluise Bagley, Dustin C. Woszczek, Grzegorz Rosenblatt, Jody Gotthardt, Michael Santis, George Parsons, Maddy 2022 Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation. Nature Communications 13 6407 1 19
dc.identifier.uri	https://hdl.handle.net/10550/87119
dc.description.abstract	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.
dc.language.iso	eng
dc.relation.ispartof	Nature Communications, 2022, vol. 13, num. 6407, p. 1-19
dc.subject	Bioquímica
dc.subject	Biologia
dc.title	Epithelial coxsackievirus adenovirus receptor promotes house dust mite-induced lung inflammation.
dc.type	journal article
dc.date.updated	2023-05-30T11:27:44Z
dc.identifier.doi	10.1038/s41467-022-33882-w
dc.identifier.idgrec	159405
dc.rights.accessRights	open access