{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:17:21Z","timestamp":1789766241133,"version":"4.0.1"},"reference-count":20,"publisher":"Korean Rhinologic Society","issue":"2","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6-2024-0183"],"award-info":[{"award-number":["6-2024-0183"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["j-rhinology.org"],"crossmark-restriction":true},"short-container-title":["J Rhinol"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"Background and Objectives: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease, classified into eosinophilic and non-eosinophilic subtypes. Although CD4<sup>+<\/sup> tissue-resident memory T (T<sub>RM<\/sub>) cells play diverse roles in tissue homeostasis, their phenotypic and functional characteristics in the nasal tissue of patients with eosinophilic CRS (ECRS) remain poorly defined.Methods: Nasal polyp tissue and\/or peripheral blood (PB) samples were obtained from patients with ECRS undergoing endoscopic sinus surgery. The phenotypes and functions of nasal CD69<sup>+<\/sup> CD4<sup>+<\/sup> T cells were analyzed using flow cytometry.Results: The frequency of CD69<sup>+<\/sup> CD103<sup>\u2013<\/sup> cells among nasal CD4<sup>+<\/sup> T cells was significantly higher in patients with ECRS compared to controls. Analysis of paired PB and nasal tissue samples from ECRS patients revealed that CD69<sup>+<\/sup> CD103<sup>\u2013<\/sup> CD4<sup>+<\/sup> T cells were almost exclusively present in nasal tissues and exhibited tissue-resident phenotypes, marked by high expression of CD49a and CXCR6. In ECRS, these nasal CD69<sup>+<\/sup> CD103<sup>\u2013<\/sup> CD4<sup>+<\/sup> T cells expressed high levels of T helper 2 (Th2) cell markers, including CRTH2 and GATA3. Consistently, these T cells demonstrated a robust capacity to produce IL-4 and IL-5. These findings were corroborated by analyses of publicly available single-cell RNA sequencing datasets. Furthermore, the frequency of nasal CD69<sup>+<\/sup> CD103<sup>\u2013<\/sup> CD4<sup>+<\/sup> T cells was significantly associated with higher Lund-Mackay CT scores and reduced olfactory function in patients with ECRS.Conclusion: The current investigation demonstrates that nasal CD69<sup>+<\/sup> CD103<sup>\u2013<\/sup> CD4<sup>+<\/sup> T<sub>RM<\/sub> cells include a high frequency of Th2 cells and are associated with severe disease.<\/jats:p>","DOI":"10.18787\/jr.2025.00025","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T23:43:15Z","timestamp":1753227795000},"page":"91-98","update-policy":"https:\/\/doi.org\/10.18787\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phenotypic Analysis of Nasal CD69+ CD4+ Tissue-Resident Memory T Cells in Eosinophilic Chronic Rhinosinusitis With Nasal Polyps"],"prefix":"10.18787","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1426-7534","authenticated-orcid":true,"given":"Min-Seok","family":"Rha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-1446","authenticated-orcid":true,"given":"Gyeongyeob","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"7989","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00218-1"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.02.016"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3390\/cells13231947"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2024.16.6.585"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.3"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aas9673"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13201"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101320-020220"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1111\/all.16094"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.05.017"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.06.023"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.21053\/ceo.2020.00864"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.07.037"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52689-5"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01312-0"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2972::aid-immu2972>3.0.co;2-#"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.118"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00750-4"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf9393"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/372190a0"}],"container-title":["Journal of Rhinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/j-rhinology.org\/upload\/pdf\/jr-2025-00025.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/j-rhinology.org\/journal\/view.php?doi=10.18787\/jr.2025.00025","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/j-rhinology.org\/upload\/pdf\/jr-2025-00025.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T04:35:52Z","timestamp":1772512552000},"score":1,"resource":{"primary":{"URL":"http:\/\/j-rhinology.org\/journal\/view.php?doi=10.18787\/jr.2025.00025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,31]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,7]]}},"URL":"https:\/\/doi.org\/10.18787\/jr.2025.00025","relation":{},"ISSN":["1229-1498","2384-4361"],"issn-type":[{"value":"1229-1498","type":"print"},{"value":"2384-4361","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,31]]},"assertion":[{"value":"2025-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-22","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-31","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}