{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:10:57Z","timestamp":1790867457328,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004710","name":"Fondazione Umberto Veronesi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["27022"],"award-info":[{"award-number":["27022"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic juvenile idiopathic arthritis (sJIA) is a chronic childhood disease classically attributed to innate immune cell dysregulation. This study aimed to elucidate the role of innate lymphoid cells (ILCs), including natural killer (NK) cells and helper\u2010ILCs (hILCs), in sJIA during clinically inactive disease (CID) through phenotypic and functional analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral ILCs from children with sJIA during CID receiving interleukin\u20101 (IL\u20101) inhibitors (n = 40) were analyzed by flow cytometry and compared to 23 healthy children (HC) and 22 patients with unrelated autoinflammatory diseases taking IL\u20101 inhibitors. Plasma proteomic profiling was also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with sJIA showed a significant reduction in circulating NK cell frequencies compared to HC, with an increased proportion of CD56<jats:sup>bright<\/jats:sup> NK cells. Although overall hILC frequencies were comparable to HC, ILC1s were increased, whereas ILC precursors were reduced. ILC1 frequency correlated positively with IL\u201018 plasma levels, whereas ILC2 frequency correlated negatively. Functional assessments revealed that NK cells from patients with sJIA had variable interferon \u03b3 (IFN\u03b3) production upon IL\u201018\/IL\u201012 stimulation, inversely correlating with IL\u201018 levels. Additionally, hILCs from these patients showed a specific impairment in IFN\u03b3 production despite normal IL\u201013 production, potentially linked to decreased IL\u201018 receptor \u03b1 expression in ILC1s. Proteomic analysis confirmed IL\u201018 as the most up\u2010regulated cytokine in sJIA plasma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with sJIA in CID exhibit significant innate immune abnormalities, including altered ILC subset distribution and impaired IFN\u03b3 production, strongly associated with IL\u201018 levels. These findings suggest ongoing immune dysregulation despite clinical remission, underscoring a potential role for ILCs and cytokine interaction in sJIA pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.43217","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T01:14:05Z","timestamp":1747098845000},"page":"1442-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Innate Lymphoid Cell Phenotypic and Functional Alterations in Patients With Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6994-2595","authenticated-orcid":false,"given":"Linda","family":"Quatrini","sequence":"first","affiliation":[{"name":"Innate Lymphoid Cells Unit Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome 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Clinical Immunology and Vaccinology Bambino Ges\u00f9 Children's Hospital, IRCCS and Department of Systems Medicine, University of Rome \u201cTor Vergata,\u201d Rome  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Clinical and Research Unit of Clinical Immunology and Vaccinology, Bambino Ges\u00f9 Children's Hospital, IRCCS and PhD Program in Immunology, Molecular Medicine and Applied Biotechnology, University of Rome \u201cTor Vergata,\u201d Rome  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Palma","sequence":"additional","affiliation":[{"name":"Clinical and Research Unit of Clinical Immunology and Vaccinology Bambino Ges\u00f9 Children's Hospital, IRCCS and Department of Systems Medicine, University of Rome \u201cTor Vergata,\u201d Rome  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