{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:22:14Z","timestamp":1780464134616,"version":"3.54.1"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T00:00:00Z","timestamp":1497225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GM08100"],"award-info":[{"award-number":["01GM08100"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010AR\u2010059049"],"award-info":[{"award-number":["R01\u2010AR\u2010059049"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic\u2010onset juvenile idiopathic arthritis (JIA) is speculated to follow a biphasic course, with an initial systemic disease phase driven by innate immune mechanisms and interleukin\u20101\u03b2 (IL\u20101\u03b2) as a key cytokine and a second chronic arthritic phase that may be dominated by adaptive immunity and cytokines such as IL\u201017A. Although a recent mouse model points to a critical role of IL\u201017\u2013expressing \u03b3\/\u03b4 T cells in disease pathology, in humans, both the prevalence of IL\u201017 and the role of IL\u201017\u2013producing cells are still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Serum samples from systemic JIA patients and healthy pediatric controls were analyzed for the levels of IL\u201017A and related cytokines. Whole blood samples were studied for cellular expression of IL\u201017 and interferon\u2010\u03b3 (IFN\u03b3). CD4+ and \u03b3\/\u03b4 T cells isolated from the patients and controls were assayed for cytokine secretion in different culture systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IL\u201017A was prevalent in sera from patients with active systemic JIA, while both ex vivo and in vitro experiments revealed that \u03b3\/\u03b4 T cells overexpressed this cytokine. This was not seen with CD4+ T cells, which expressed strikingly low levels of IFN\u03b3. Therapeutic IL\u20101 blockade was associated with partial normalization of both cytokine expression phenotypes. Furthermore, culturing healthy donor \u03b3\/\u03b4 T cells in serum from systemic JIA patients or in medium spiked with IL\u20101\u03b2, IL\u201018, and S100A12 induced IL\u201017 overexpression at levels similar to those observed in the patients' cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A systemic JIA cytokine environment may prime \u03b3\/\u03b4 T cells in particular for IL\u201017A overexpression. Thus, our observations in systemic JIA patients strongly support a pathophysiologic role of these cells, as proposed by the recent murine model.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40099","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T11:12:58Z","timestamp":1489576378000},"page":"1480-1494","source":"Crossref","is-referenced-by-count":84,"title":["Proinflammatory Cytokine Environments Can Drive Interleukin\u201017 Overexpression by \u03b3\/\u03b4 T Cells in Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"69","author":[{"given":"Christoph","family":"Kessel","sequence":"first","affiliation":[{"name":"University Children's Hospital M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Lippitz","sequence":"additional","affiliation":[{"name":"University Children's Hospital M\u00fcnster 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