{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:17:02Z","timestamp":1790709422697,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100020480","name":"CSL Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020480","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1142013"],"award-info":[{"award-number":["GNT1142013"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT2004288"],"award-info":[{"award-number":["GNT2004288"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Asthma\u2010COPD overlap (ACO) is characterized by patients exhibiting features of both asthma and COPD. Currently, there is no specific treatment for ACO. This study aimed to investigate the therapeutic potential of targeting CD131, a shared receptor subunit for IL\u20103, IL\u20105 and GM\u2010CSF, in ACO development and in preventing acute viral exacerbations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A two\u2010hit mouse model of ACO was established by house dust mite (HDM) allergen sensitization to model asthma, and elastase treatment to model emphysema. In a separate model, human rhinovirus 1b (RV1b) was used to induce an acute asthma exacerbation. A neutralizing antibody against CD131 was used to block CD131 in vivo signalling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice exposed to HDM and elastase developed cardinal features for asthma and COPD, including airway hyperreactivity (AHR) and emphysema. A mixed granulocytic inflammatory profile was identified in the lungs, including expansion of monocyte\u2010derived macrophages, neutrophils and eosinophils. RT\u2010qPCR analysis detected heightened gene expression of <jats:italic>Mmp12<\/jats:italic>, <jats:italic>Il5<\/jats:italic> and <jats:italic>Il13<\/jats:italic>. Transcriptomic analysis further revealed pathway enrichment for type 2 inflammation and macrophage activation. Blockade of CD131 effectively reduced the lung inflammation and prevented the development of AHR, airway fibrosis and emphysema. Interestingly, pathway enrichment for Th1 response and interferon production detected in the model was not affected by the treatment. Consistently, CD131 antagonism prevented RV1b\u2010induced asthma exacerbation without compromising RV1b clearance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CD131 signalling coordinates multiple pathological pathways that drive airway inflammation and lung remodelling in ACO. Hence, CD131 antagonism represents a novel approach to combating the immunopathology in the complex ACO setting.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.14877","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T03:35:44Z","timestamp":1736998544000},"page":"303-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp>CD131<\/scp> antagonism blocks inflammation, emphysema and fibrosis in an asthma\u2010<scp>COPD<\/scp> overlap mouse model originating in early life"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0901-5183","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Melbourne Victoria Australia"},{"name":"Centre for Respiratory Science &amp; Health  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nok Him","family":"Fung","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences RMIT University  Melbourne Victoria Australia"},{"name":"Centre for Respiratory Science &amp; 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