RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

Arikkatt, J; Ullah, MA; Short, KR; Zhang, V; Gan, WJ; Loh, Z; Werder, RB; Simpson, J; Sly, PD; Mazzone, SB; Spann, KM; Ferreira, MAR; Upham, JW; Sukkar, MB; Phipps, S

RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

Arikkatt, J Ullah, MA Short, KR Zhang, V Gan, WJ Loh, Z Werder, RB Simpson, J Sly, PD Mazzone, SB Spann, KM Ferreira, MAR Upham, JW Sukkar, MB

Phipps, S

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Publication Type:: Journal Article
Citation:: eLife, 2017, 6
Issue Date:: 2017-01-18

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Field	Value	Language
dc.contributor.author	Arikkatt, J	en_US
dc.contributor.author	Ullah, MA	en_US
dc.contributor.author	Short, KR	en_US
dc.contributor.author	Zhang, V	en_US
dc.contributor.author	Gan, WJ	en_US
dc.contributor.author	Loh, Z	en_US
dc.contributor.author	Werder, RB	en_US
dc.contributor.author	Simpson, J	en_US
dc.contributor.author	Sly, PD	en_US
dc.contributor.author	Mazzone, SB	en_US
dc.contributor.author	Spann, KM	en_US
dc.contributor.author	Ferreira, MAR	en_US
dc.contributor.author	Upham, JW	en_US
dc.contributor.author	Sukkar, MB https://orcid.org/0000-0003-4591-2399	en_US
dc.contributor.author	Phipps, S	en_US
dc.date.available	2017-01-03	en_US
dc.date.issued	2017-01-18	en_US
dc.identifier.citation	eLife, 2017, 6	en_US
dc.identifier.uri	http://hdl.handle.net/10453/115191
dc.description.abstract	© 2017, eLife Sciences Publications Ltd. All rights reserved. Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target.	en_US
dc.relation.ispartof	eLife	en_US
dc.relation.isbasedon	10.7554/eLife.21199	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Murine pneumonia virus	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Agranulocytosis	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	HMGB1 Protein	en_US
dc.subject.mesh	Receptor for Advanced Glycation End Products	en_US
dc.subject.mesh	Viral Load	en_US
dc.title	RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Graduate School of Health
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

© 2017, eLife Sciences Publications Ltd. All rights reserved. Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of individuals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM; a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target.

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http://hdl.handle.net/10453/115191