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The CD131 receptor is indispensable for signalling by the \u03b2 common (\u03b2c) family of cytokines encompassing granulocyte\u2212macrophage colony-stimulating factor, interleukin (IL)-5 and IL-3, which instigate both type-2 and non-type-2 inflammatory responses. This study aims to determine whether antagonising CD131 signalling can prevent pulmonary inflammation, alveolar cell death and emphysema development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed in-house and<jats:italic>in silico<\/jats:italic>transcriptomic analysis to investigate the gene expression of CD131 (<jats:italic>CSF2RB<\/jats:italic>) and pathway enrichment for \u03b2c cytokine signalling in blood, sputum and lung biopsies of COPD patients. To model emphysema, transgenic mice expressing human CD131 were exposed to elastase or cigarette smoke (CS) and a fully human monoclonal antibody (CSL311) was employed to inhibit CD131 signalling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CD131 gene expression was significantly increased in COPD, along with an enrichment of gene set for \u03b2c cytokine signalling. In transgenic mice subjected to emphysema models, CD131 antagonism effectively prevented lung injury, alveolar cell death and emphysema development. Mechanistically, RNA sequencing identified pathway enrichment for myeloid cell activation, type-2 immune response and macrophage alternative activation in elastase-induced emphysematous mice, mirroring human COPD. Blocking CD131 signalling almost completely reversed the global gene expression alterations associated with emphysema development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CD131 signalling orchestrates pulmonary inflammation in COPD, resulting in immunopathology that underpins emphysema and lung function decline. Antagonising CD131 therefore represents a unique strategy to simultaneously target multiple pathogenic myeloid cell populations.<\/jats:p><\/jats:sec>","DOI":"10.1183\/23120541.01020-2024","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T01:20:29Z","timestamp":1736385629000},"page":"01020-2024","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Signalling<i>via<\/i>CD131 regulates pulmonary inflammation, alveolar cell death and emphysema in COPD"],"prefix":"10.1183","volume":"11","author":[{"given":"Hao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nok 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