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Coxsackievirus Adenovirus Receptor co-ordinates pro-inflammatory responses in the lung epithelium

ABSTRACT: Airway inflammation and remodelling are key pathophysiologic features process in many respiratory conditions such as asthma. An intact epithelial cell layer is crucial to maintain lung homeostasis, and this depends on intercellular adhesion. The Coxsackievirus Adenovirus Receptor (CAR) is highly expressed in the epithelium where it modulates cell-cell adhesion stability and acts as a receptor for immune cells to facilitate transepithelial migration. Here we investigated the mechanistic role 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, decreased IL-4 and IL-13 levels and reduced matrix remodelling. In vitro analysis in human lung epithelial cells confirmed that loss of CAR led to reduced HDM-dependent inflammatory cytokine release leading to reduced inflammatory cell transmigration. Moreover, CAR was required for HDM-induced TGF release leading to enhanced airway smooth muscle cell proliferation and matrix production. Our data demonstrates that CAR is a novel central co-ordinator of lung inflammation through a dual role in leukocyte recruitment and tissue remodelling and may represent an important target for future therapeutic development in lung inflammatory diseases.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Marieluise Kirchner

LAB HEAD: Philipp Mertins

PROVIDER: PXD029237 | Pride | 2022-09-20

REPOSITORIES: Pride

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			Action	DRS
	BiotinSites.txt	Txt
	BirA_CAR.fasta	Fasta
	Deamidation__NQ_Sites.txt	Txt
	Oxidation__M_Sites.txt	Txt
	Statler_20210203_SN_HS_bioID_01_C5.raw	Raw

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