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RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma
journal contribution
posted on 2017-01-18, 00:00 authored by J Arikkatt, M A Ullah, K R Short, V Zhang, W J Gan, Z Loh, R B Werder, J Simpson, Peter Sly, S B Mazzone, K M Spann, M A R Ferreira, J W Upham, M B Sukkar, S PhippsAsthma 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.
History
Journal
eLifeVolume
6Article number
e21199Publisher
eLife Sciences PublicationsLocation
Cambridge, Eng.Publisher DOI
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ISSN
2050-084XeISSN
2050-084XLanguage
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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BiologyDENDRITIC CELLSHMGB1 PROTEININFLAMMATORY SUBTYPESINNATE LYMPHOID-CELLSLife Sciences & BiomedicinePATHOGENESISPATHWAYPNEUMONIA VIRUSPNEUMOVIRUS INFECTIONRECEPTORScience & TechnologyLife Sciences & Biomedicine - Other TopicsSMOOTH-MUSCLEHMGB1RAGEasthmaimmunologyinfectious diseasemicrobiologymousepaucigranulocyticvirus infection
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