{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:00:27Z","timestamp":1789419627300,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,8,27]],"date-time":"2009-08-27T00:00:00Z","timestamp":1251331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Systemic\u2010onset juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by arthritis and systemic features. Its pathogenesis is still largely unknown. It is characterized immunologically by natural killer (NK) cell dysfunction and cytokine signatures that predominantly feature interleukin\u20101 (IL\u20101), IL\u20106, and IL\u201018. Since IL\u201018 can drive NK cell function, we examined how the high plasma levels of this cytokine are related to the documented NK cell failure in these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The phenotype and function of NK cells from 10 healthy control subjects, 15 patients with polyarticular JIA, and 15 patients with systemic\u2010onset JIA were characterized by staining and functional assays in vitro. IL\u201018 ligand binding was visualized by fluorescence microscopy. Phosphorylation of several MAP kinases and the IL\u201018 receptor \u03b2 (IL\u201018R\u03b2) were visualized by Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IL\u201018 from the plasma of systemic\u2010onset JIA patients stimulated the activation of NK cells from healthy controls and bound its cognate receptor. However, NK cells from systemic\u2010onset JIA patients failed to up\u2010regulate cell\u2010mediated killing molecules, such as perforin and interferon\u2010\u03b3, after IL\u201018 stimulation. Furthermore, treatment with IL\u201018 did not induce the phosphorylation of receptor\u2010activated MAP kinases in NK cells. Alternate activation of NK cells by IL\u201012 induced NK cell cytotoxicity. We observed no additive effect of IL\u201018 in combination with IL\u201012 in systemic\u2010onset JIA patients. Immunoprecipitation of IL\u201018R\u03b2 showed that NK cells from systemic\u2010onset JIA could not phosphorylate this receptor after IL\u201018 stimulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The mechanism of the impaired NK cell function in systemic\u2010onset JIA involves a defect in IL\u201018R\u03b2 phosphorylation. This observation has major implications for the understanding and, ultimately, the treatment of systemic\u2010onset JIA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.24750","type":"journal-article","created":{"date-parts":[[2009,8,27]],"date-time":"2009-08-27T08:47:53Z","timestamp":1251362873000},"page":"2782-2793","source":"Crossref","is-referenced-by-count":148,"title":["Defective phosphorylation of interleukin\u201018 receptor \u03b2 causes impaired natural killer cell function in systemic\u2010onset juvenile idiopathic arthritis"],"prefix":"10.1002","volume":"60","author":[{"given":"Wilco","family":"de Jager","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan J.","family":"Vastert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey 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