{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T07:35:13Z","timestamp":1767771313765,"version":"build-2065373602"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["11K0722N","1S10618N","1S75320N","G0A3218N"],"award-info":[{"award-number":["11K0722N","1S10618N","1S75320N","G0A3218N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004497","name":"Onderzoeksraad, KU Leuven","doi-asserted-by":"publisher","award":["C16\/17\/010"],"award-info":[{"award-number":["C16\/17\/010"]}],"id":[{"id":"10.13039\/501100004497","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":[[2022,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Systemic juvenile idiopathic arthritis (JIA) is a systemic inflammatory disease with childhood onset. Systemic JIA is associated with neutrophilia, including immature granulocytes, potentially driven by the growth factor granulocyte\u2010colony stimulating factor (G\u2010CSF). This study was undertaken to investigate the role of G\u2010CSF in the pathology of systemic JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Injection of Freund's complete adjuvant (CFA) in BALB\/c mice induces mild inflammation and neutrophilia in wild\u2010type (WT) mice and a more pronounced disease, reminiscent to that of JIA patients, in interferon\u2010\u03b3\u2013knockout (IFN\u03b3\u2010KO) mice. Extramedullary myelopoiesis was studied in CFA\u2010immunized mice by single\u2010cell RNA sequencing, and the effect of G\u2010CSF receptor (G\u2010CSFR) blockage on neutrophil development and systemic JIA pathology was evaluated. Additionally, plasma G\u2010CSF levels were measured in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both in systemic JIA patients and in a corresponding mouse model, plasma G\u2010CSF levels were increased. In the mouse model, we demonstrated that G\u2010CSF is responsible for the observed neutrophilia and extramedullary myelopoiesis and the induction of immature neutrophils and myeloid\u2010derived suppressor\u2010like cells. Administration of a G\u2010CSFR antagonizing antibody blocked the maturation and differentiation of neutrophils in CFA\u2010immunized mice. In IFN\u03b3\u2010KO mice, treatment was associated with almost complete inhibition of arthritis due to reduced neutrophilia and osteoclast formation. Disease symptoms were ameliorated, but slight increases in interleukin\u20106 (IL\u20106), tumor necrosis factor, and IL\u201017 were detected upon G\u2010CSFR inhibition in the IFN\u03b3\u2010KO mice, and were associated with mild increases in weight loss, tail damage, and immature red blood cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We describe the role of G\u2010CSF in a mouse model of systemic JIA and suggest an important role for G\u2010CSF\u2013induced myelopoiesis and neutrophilia in regulating the development of arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42104","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T02:55:28Z","timestamp":1646362528000},"page":"1257-1270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role for Granulocyte <scp>Colony\u2010Stimulating<\/scp> Factor in Neutrophilic Extramedullary Myelopoiesis in a Murine Model of Systemic Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-1145","authenticated-orcid":false,"given":"Bert","family":"Malengier\u2010Devlies","sequence":"first","affiliation":[{"name":"Katholieke Universiteit (KU) Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eline","family":"Bernaerts","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit (KU) Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kourosh","family":"Ahmadzadeh","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit (KU) Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Filtjens","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit (KU) Leuven  Leuven 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