{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:34:56Z","timestamp":1788183296652,"version":"build-2803163510"},"reference-count":141,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005866","name":"Far Eastern Memorial Hospital","doi-asserted-by":"crossref","award":["FEMH-2024-C-041"],"award-info":[{"award-number":["FEMH-2024-C-041"]}],"id":[{"id":"10.13039\/501100005866","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005866","name":"Far Eastern Memorial Hospital","doi-asserted-by":"crossref","award":["FEMH-2025-C-04"],"award-info":[{"award-number":["FEMH-2025-C-04"]}],"id":[{"id":"10.13039\/501100005866","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FEMH-2024-C-041"],"award-info":[{"award-number":["FEMH-2024-C-041"]}],"id":[{"id":"https:\/\/ror.org\/019tq3436","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FEMH-2025-C-04"],"award-info":[{"award-number":["FEMH-2025-C-04"]}],"id":[{"id":"https:\/\/ror.org\/019tq3436","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Interleukin-5 (IL-5) has long been positioned as a lineage-restricted cytokine primarily responsible for eosinophil differentiation and survival. However, emerging mechanistic and clinical evidence supports a broader conceptual shift: IL-5 should no longer be viewed solely as an eosinophil growth factor, but as a context-dependent regulator embedded within dynamic airway immune networks. Drawing on advances in eosinophil subset biology, receptor signaling, and tissue-level immune crosstalk, this review reframes IL-5 biology through the lens of systems-level inflammatory regulation across airway and systemic eosinophilic diseases. Recent data reveal functional heterogeneity between resident and inflammatory eosinophil subsets, challenging the assumption that blood eosinophilia uniformly reflects pathogenic activity. In parallel, functional IL-5 receptor expression has been identified on multiple structural and immune cell populations\u2014including epithelial cells, mast cells, plasma cells, basophils, neutrophils, and fibroblasts\u2014supporting a broader tissue-signaling paradigm. Experimental and translational studies further link IL-5 to epithelial integrity, airway remodeling, and mucus pathology, suggesting structural and network-level effects beyond simple eosinophil depletion. Comparative analyses across asthma, chronic rhinosinusitis with nasal polyps, and COPD demonstrate that eosinophilic inflammation is biologically heterogeneous and context-dependent. While IL-5-targeted therapies yield consistent benefit in severe asthma, therapeutic responses in other airway diseases appear to be shaped by local tissue architecture and mixed inflammatory programs. Together, these observations illustrate a paradigm shift from pathway-specific inhibition toward network-informed disease control and highlight key areas for future mechanistic investigation.<\/jats:p>","DOI":"10.3390\/ijms27094077","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:12:09Z","timestamp":1777857129000},"page":"4077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Beyond Eosinophil Depletion: IL-5 as a Context-Dependent Regulator of Airway Immune Networks"],"prefix":"10.3390","volume":"27","author":[{"given":"Shih-Lung","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pulmonary Medicine, Far Eastern Memorial Hospital, New Taipei City 22000, Taiwan"},{"name":"Department of Chemical Engineering and Materials Science, Yuan Ze University, Taoyuan 320315, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102829","DOI":"10.1016\/j.autrev.2021.102829","article-title":"Vasculitis therapy refines vasculitis mechanistic classification","volume":"20","author":"Torp","year":"2021","journal-title":"Autoimmun. 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