RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

Arikkatt, Jaisy, Ullah, Md Ashik, Short, Kirsty Renfree, Zhang, Vivian, Gan, Wan Jun, Loh, Zhixuan, Werder, Rhiannon B., Simpson, Jennifer, Sly, Peter D., Mazzone, Stuart B., Spann, Kirsten M., Ferreira, Manuel A R., Upham, John W., Sukkar, Maria B. and Phipps, Simon (2017) RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma. eLife, 6 . doi:10.7554/eLife.21199


Author Arikkatt, Jaisy
Ullah, Md Ashik
Short, Kirsty Renfree
Zhang, Vivian
Gan, Wan Jun
Loh, Zhixuan
Werder, Rhiannon B.
Simpson, Jennifer
Sly, Peter D.
Mazzone, Stuart B.
Spann, Kirsten M.
Ferreira, Manuel A R.
Upham, John W.
Sukkar, Maria B.
Phipps, Simon
Title RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma
Journal name eLife   Check publisher's open access policy
ISSN 2050-084X
Publication date 2017-01-18
Year available 2017
Sub-type Article (original research)
DOI 10.7554/eLife.21199
Open Access Status DOI
Volume 6
Total pages 25
Place of publication Cambridge, United Kingdom
Publisher eLife Sciences Publications
Language eng
Subject 2800 Neuroscience
2700 Medicine
2400 Immunology and Microbiology
1300 Biochemistry, Genetics and Molecular Biology
Abstract 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.
Formatted abstract
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.
Keyword Biology
Life Sciences & Biomedicine - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1054081
Institutional Status UQ

 
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