{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T02:59:55Z","timestamp":1777517995078,"version":"3.51.4"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Systemic juvenile idiopathic arthritis (sJIA) is a childhood-onset immune disorder of unknown cause. One of the concepts is that the disease results from an inappropriate control of immune responses to an initially harmless trigger. In the current study, we investigated whether sJIA may be caused by defects in IL-10, a key cytokine in controlling inflammation. We used a translational approach, with an sJIA-like mouse model and sJIA patient samples. The sJIA mouse model relies on injection of CFA in IFN-\u03b3\u2013deficient BALB\/c mice; corresponding wild type (WT) mice only develop a subtle and transient inflammatory reaction. Diseased IFN-\u03b3\u2013deficient mice showed a defective IL-10 production in CD4+ regulatory T cells, CD19+ B cells, and CD3\u2212CD122+CD49b+ NK cells, with B cells as the major source of IL-10. In addition, neutralization of IL-10 in WT mice resulted in a chronic immune inflammatory disorder clinically and hematologically reminiscent of sJIA. In sJIA patients, IL-10 plasma levels were strikingly low as compared with proinflammatory mediators. Furthermore, CD19+ B cells from sJIA patients showed a decreased IL-10 production, both ex vivo and after in vitro stimulation. In conclusion, IL-10 neutralization in CFA-challenged WT mice converts a transient inflammatory reaction into a chronic disease and represents an alternative model for sJIA in IFN-\u03b3\u2013competent mice. Cell-specific IL-10 defects were observed in sJIA mice and patients, together with an insufficient IL-10 production to counterbalance their proinflammatory cytokines. Our data indicate that a defective IL-10 production contributes to the pathogenesis of sJIA.<\/jats:p>","DOI":"10.4049\/jimmunol.1800468","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T14:17:17Z","timestamp":1538144237000},"page":"2654-2663","source":"Crossref","is-referenced-by-count":25,"title":["Insufficient IL-10 Production as a Mechanism Underlying the Pathogenesis of Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4467-9831","authenticated-orcid":false,"given":"Maya","family":"Imbrechts","sequence":"first","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneleen","family":"Avau","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Vandenhaute","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-1145","authenticated-orcid":false,"given":"Bert","family":"Malengier-Devlies","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Put","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Mitera","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nele","family":"Berghmans","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-7373","authenticated-orcid":false,"given":"Oliver","family":"Burton","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Genetics of Autoimmunity, VIB Center for Brain and Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0491-6887","authenticated-orcid":false,"given":"Steffie","family":"Junius","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Genetics of Autoimmunity, VIB Center for Brain and Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-4085","authenticated-orcid":false,"given":"Adrian","family":"Liston","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Genetics of Autoimmunity, VIB Center for Brain and Disease Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lien","family":"de Somer","sequence":"additional","affiliation":[{"name":"University Hospital Leuven, Laboratory of Pediatric Immunology , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Wouters","sequence":"additional","affiliation":[{"name":"University Hospital Leuven, Laboratory of Pediatric Immunology , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Matthys","sequence":"additional","affiliation":[{"name":"KU Leuven, Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,11,1]]},"reference":[{"key":"2025030417574040500_r1","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/nrrheum.2011.68","article-title":"Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions","volume":"7","author":"Mellins","year":"2011","journal-title":"Nat. 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