{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:36:12Z","timestamp":1792427772614,"version":"4.5.0"},"reference-count":163,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The nasal mucosa functions as a highly specialized barrier that integrates epithelial, stromal, neuronal, and immune signals to maintain homeostasis and mount rapid responses to environmental challenges. Among its resident immune populations, innate lymphoid cells\u2014particularly type 2 ILCs (ILC2s)\u2014play a pivotal role in orchestrating type 2 inflammation driven by epithelial-derived alarmins such as IL-25, IL-33, and TSLP. Upon activation, ILC2s release IL-5 and IL-13, promoting eosinophilic inflammation, goblet cell hyperplasia, mucus hypersecretion, and tissue remodeling, all central features of chronic rhinosinusitis with nasal polyps (CRSwNP) and severe allergic rhinitis. Recent advances have revealed substantial ILC plasticity, the presence of nasal-resident ILC progenitors, and the influence of metabolic and neuroimmune cues in shaping ILC activation and persistence. Dupilumab, a monoclonal antibody targeting IL-4R\u03b1, has emerged as a highly effective therapy, providing unique mechanistic insight into the epithelial\u2013ILC axis. By blocking IL-4\/IL-13 signaling, dupilumab dampens ILC2 effector functions, reduces IL-5\/IL-13 output, restores epithelial barrier integrity, interrupts alarmin-driven amplification loops, and rebalances innate and adaptive immune networks. Clinical and translational studies indicate that baseline ILC2 phenotypes\u2014particularly inflammatory ILC2 subsets\u2014may predict treatment responsiveness, positioning ILC profiling as a promising biomarker strategy. This review synthesizes current knowledge of ILC classification, plasticity, progenitor biology, and epithelial\u2013ILC communication in the nasal mucosa, while integrating emerging evidence on dupilumab-mediated immunomodulation. Collectively, these insights highlight ILCs as central drivers of type 2 inflammation and key targets for precision immunomodulation, offering a framework for personalized treatment approaches in CRSwNP and allergic rhinitis.<\/jats:p>","DOI":"10.3390\/ijms27041992","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T11:44:27Z","timestamp":1771501467000},"page":"1992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Mucosal Remodeling in Chronic Rhinosinusitis with Nasal Polyps: The Role of Innate Lymphoid Cells and Reprogramming Under IL-4R\u03b1 Blockade"],"prefix":"10.3390","volume":"27","author":[{"given":"Giovanna Lucia","family":"Piazzetta","sequence":"first","affiliation":[{"name":"Otolaryngology Head and Neck Surgery, Department of Medical and Surgical Sciences, University \u201cMagna Gr\u00e6cia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Lobello","sequence":"additional","affiliation":[{"name":"Otolaryngology Head and Neck Surgery, Department of Medical and Surgical Sciences, University \u201cMagna Gr\u00e6cia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3730-1125","authenticated-orcid":false,"given":"Silvia","family":"Di Agostino","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Coscarella","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4236-7367","authenticated-orcid":false,"given":"Corrado","family":"Pelaia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8294-8684","authenticated-orcid":false,"given":"Anna","family":"Di Vito","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Bria","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6184-5126","authenticated-orcid":false,"given":"Andrea","family":"Filardo","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Aloisio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8786-3489","authenticated-orcid":false,"given":"Chiara","family":"Lupia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, 87100 Cosenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8314-715X","authenticated-orcid":false,"given":"Emanuela","family":"Chiarella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University \u201cMagna Graecia\u201d, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/JVI.00130-21","article-title":"Human Nasal and Lung Tissues Infected Ex Vivo with SARS-CoV-2 Provide Insights into Differential Tissue-Specific and Virus-Specific Innate Immune Responses in the Upper and Lower Respiratory Tract","volume":"95","author":"Alfi","year":"2021","journal-title":"J. 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