{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T18:20:19Z","timestamp":1775672419013,"version":"3.50.1"},"reference-count":75,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Respiratory syncytial virus (RSV) infection induces asthma exacerbations, which leads to worsening of clinical symptoms and may result in a sustained decline in lung function. Exacerbations are the main cause of morbidity and mortality associated with asthma, and significantly contribute to asthma-associated healthcare costs. Although glucocorticoids are used to manage exacerbations, some patients respond to them poorly. The underlying mechanisms associated with steroid-resistant exacerbations remain largely unknown. We have previously established a mouse model of RSV-induced exacerbation of allergic airways disease, which mimics hallmark clinical features of asthma. In this study, we have identified key roles for macrophage IFN-\u03b3 and IL-27 in the regulation of RSV-induced exacerbation of allergic airways disease. Production of IFN-\u03b3 and IL-27 was steroid-resistant, and neutralization of IFN-\u03b3 or IL-27 significantly suppressed RSV-induced steroid-resistant airway hyperresponsiveness and airway inflammation. We have previously implicated activation of pulmonary macrophage by TNF-\u03b1 and\/or MCP-1 in the mechanisms of RSV-induced exacerbation. Stimulation of pulmonary macrophages with TNF-\u03b1 and\/or MCP-1 induced expression of both IFN-\u03b3 and IL-27. Our findings highlight critical roles for IFN-\u03b3 and IL-27, downstream of TNF-\u03b1 and MCP-1, in the mechanism of RSV-induced exacerbation. Thus, targeting the pathways that these factors activate may be a potential therapeutic approach for virus-induced asthma exacerbations.<\/jats:p>","DOI":"10.4049\/jimmunol.1601950","type":"journal-article","created":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T16:15:25Z","timestamp":1511367325000},"page":"237-247","source":"Crossref","is-referenced-by-count":30,"title":["Identification of IFN-\u03b3 and IL-27 as Critical Regulators of Respiratory Syncytial Virus\u2013Induced Exacerbation of Allergic Airways Disease in a Mouse Model"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4307-1987","authenticated-orcid":false,"given":"Thi Hiep","family":"Nguyen","sequence":"first","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]},{"name":"Hunter Medical Research Institute , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1240-5964","authenticated-orcid":false,"given":"Steven","family":"Maltby","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]},{"name":"Hunter Medical Research Institute , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hock L","family":"Tay","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]},{"name":"Hunter Medical Research Institute , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Eyers","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]},{"name":"Hunter Medical Research Institute , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul S","family":"Foster","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]},{"name":"Hunter Medical Research Institute , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Priority Research Centre for Healthy Lungs, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]},{"name":"Hunter Medical Research Institute , Callaghan, New South Wales 2308, ; and , New Lambton Heights, New South Wales 2305,","place":["Australia Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,1,1]]},"reference":[{"key":"2025030610003168300_r1","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/S0140-6736(10)60206-1","article-title":"Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis","volume":"375","author":"Nair","year":"2010","journal-title":"Lancet"},{"key":"2025030610003168300_r2","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1086\/430008","article-title":"Respiratory syncytial virus load predicts disease severity in previously healthy infants","volume":"191","author":"DeVincenzo","year":"2005","journal-title":"J. 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