{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:21:35Z","timestamp":1780500095769,"version":"3.54.1"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Publication Fund of the University of Wuerzburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ARM"],"abstract":"<jats:p>(1) Background: Innate lymphoid cells (ILCs) are potent cytokine producers that regulate local immune responses in tissues. Natural killer (NK) cells belong to group 1 ILCs and play an important role in tumor clearance and defense against intracellular pathogens. ILC2 and 3 have been implied in allergic responses and other chronic inflammatory diseases. The role of these cells in the pathogenesis of chronic rhinosinusitis (CRS) is not completely understood. There are changes in the cellular infiltrate in the mucosa of patients with CRS with and without polyps. The aim of this study was to characterize the number and phenotype of NK cells, ILC2s and ILC3s in patients with CRS. (2) Methods: Tissue samples were collected from patients with CRS with and without nasal polyps who were undergoing nasal sinus surgery as well as control patients who were undergoing surgery due to non-inflammatory reasons. Lymphocytes were isolated from the tissues using mechanical and enzymatic dissociation. Peripheral blood lymphocytes were obtained from the same patients. All cells were examined by multicolor flow cytometry. NK cells were analyzed for the distribution of CD56dimCD16+ and CD56brightCD16\u2212 subsets and the expression of IL18R\u03b1, CD16, CD57, GATA3, TCF1 and NKp44. In ILC2s, GATA3 and IL18R\u03b1 expression was determined, and ILC3s as well as NKp44+ and NKp44\u2212ILC3 subsets were analyzed for the expression of IL18R\u03b1. (3) Results: There were significantly fewer NK cells in the nasal polyps compared to the peripheral blood of patients with CRSwNP and tissues from CRSsNP patients, which both showed higher levels of TCF1 expression. Irrespective of the disease condition, NK cells in tissues showed lower CD16 expression and a lower frequency of the CD56dimCD16+ subset compared to the peripheral blood mononuclear cells. Additionally, a smaller percentage of NK cells were terminally matured, as measured by CD16+ and CD57+ expression, in all examined nasal mucosa tissues. In the tissue ILC3s, we predominantly found cells from the NKp44\u2212 subset in all groups. ILC3s from CRSsNP patients showed the highest frequencies of IL18R\u03b1+ cells of all examined tissues. ILC2s from the polyps ofCRSwNP patients showed higher levels of GATA3 expression than their peripheral blood counterparts. (4) Conclusions: We found that tissue-resident NK cells in mucosa from the nose and sinuses are a more heterogenous and less mature population than those in peripheral blood. Expression of the examined markers in NK cells was similar among groups. NK cell frequency, both in blood and tissue from CRSsNP patients, was higher than in the other groups, indicating that these cells might play an important role in this phenotype. Changes in the IL18R\u03b1 expression of ILC3s suggest a potential role of IL18 signaling in CRS pathogenesis.<\/jats:p>","DOI":"10.3390\/arm94030035","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:46:48Z","timestamp":1780494408000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Innate Lymphoid Cells in Chronic Rhinosinusitis: Insights from Tissue and Peripheral Blood Flow Cytometric Analysis"],"prefix":"10.3390","volume":"94","author":[{"given":"Rina","family":"Hoffmann","sequence":"first","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Wuerzburg, 97074 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Rombach","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Wuerzburg, 97074 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-4133","authenticated-orcid":false,"given":"Jens","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Wuerzburg, 97074 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-5995","authenticated-orcid":false,"given":"Agmal","family":"Scherzad","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Wuerzburg, 97074 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6995-1849","authenticated-orcid":false,"given":"Stephan","family":"Hackenberg","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Wuerzburg, 97074 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8775-1330","authenticated-orcid":false,"given":"Pascal","family":"Ickrath","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology, Head and Neck Surgery, University of Wuerzburg, 97074 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"EPOS2020: A major step forward","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. 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