{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:24:25Z","timestamp":1761920665846,"version":"3.38.0"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,12,1]],"date-time":"2019-12-01T00:00:00Z","timestamp":1575158400000},"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":[[2019,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mice deficient in IFN-\u03b3 (IFN-\u03b3 knockout [KO] mice) develop a systemic inflammatory syndrome in response to CFA, in contrast to CFA-challenged wild-type (WT) mice who only develop a mild inflammation. Symptoms in CFA-challenged IFN-\u03b3 KO resemble systemic juvenile idiopathic arthritis (sJIA), a childhood immune disorder of unknown cause. Dysregulation of innate immune cells is considered to be important in the disease pathogenesis. In this study, we used this murine model to investigate the role of NK cells in the pathogenesis of sJIA. NK cells of CFA-challenged IFN-\u03b3 KO mice displayed an aberrant balance of activating and inhibitory NK cell receptors, lower expression of cytotoxic proteins, and a defective NK cell cytotoxicity. Depletion of NK cells (via anti\u2013IL-2R\u03b2 and anti\u2013Asialo-GM1 Abs) or blockade of the NK cell activating receptor NKG2D in CFA-challenged WT mice resulted in increased severity of systemic inflammation and appearance of sJIA-like symptoms. NK cells of CFA-challenged IFN-\u03b3 KO mice and from anti-NKG2D\u2013treated mice showed defective degranulation capacities toward autologous activated immune cells, predominantly monocytes. This is in line with the increased numbers of activated inflammatory monocytes in these mice which was particularly reflected in the expression of CCR2, a chemokine receptor, and in the expression of Rae-1, a ligand for NKG2D. In conclusion, NK cells are defective in a mouse model of sJIA and impede disease development in CFA-challenged WT mice. Our findings point toward a regulatory role for NK cells in CFA-induced systemic inflammation via a NKG2D-dependent control of activated immune cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1900510","type":"journal-article","created":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T20:55:17Z","timestamp":1572641717000},"page":"3339-3348","source":"Crossref","is-referenced-by-count":21,"title":["Regulatory Role for NK Cells in a Mouse Model of Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-8806","authenticated-orcid":false,"given":"Jessica","family":"Vandenhaute","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anneleen","family":"Avau","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Filtjens","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 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":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4467-9831","authenticated-orcid":false,"given":"Maya","family":"Imbrechts","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0026-4498","authenticated-orcid":false,"given":"Nathalie","family":"Van den Berghe","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3155-7509","authenticated-orcid":false,"given":"Kourosh","family":"Ahmadzadeh","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Mitera","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Boon","sequence":"additional","affiliation":[{"name":"Bioceros , 3584 Utrecht ,","place":["the Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1691-5294","authenticated-orcid":false,"given":"Georges","family":"Leclercq","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Microbiology and Immunology, Ghent University , 9000 Ghent ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carine","family":"Wouters","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]},{"name":"Division of Pediatric Rheumatology, University Hospitals Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-6836","authenticated-orcid":false,"given":"Patrick","family":"Matthys","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven , 3000 Leuven ,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"2025030417544690700_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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