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Given the fundamental role of monocyte activation in remodeling the early phases of inflammatory responses, here we analyze the GM\u2010CSF\/IFN\u2010\u03b3 induced activity of human monocytes in such a situation in vitro and in vivo. Monocytes from healthy donors were isolated and stimulated with GM\u2010CSF\u00a0\u00b1\u00a0IFN\u2010\u03b3. Monocyte activation and death were analyzed by flow cytometry, immunofluorescence microscopy, ELISA, and qPCR. T\u2010cell GM\u2010CSF\/IFN\u2010\u03b3 expression and monocyte function were determined in synovial fluid and peripheral blood from 15 patients with active JIA and 21 healthy controls. Simultaneous treatment with GM\u2010CSF and IFN\u2010\u03b3 induces cell death of monocytes. This cell death is partly cathepsin B\u2010associated and has morphological characteristics of necrosis. Monocytes responding to costimulation with strong proinflammatory activities are consequently eliminated. Monocytes surviving this form of hyperactivation retain normal cytokine production. Cathepsin B activity is increased in monocytes isolated from synovial fluid from patients with active arthritis. Our data suggest GM\u2010CSF\/IFN\u2010\u03b3 induced cell death of monocytes as a novel mechanism to eliminate overactivated monocytes, thereby potentially balancing inflammation and autoimmunity in JIA.<\/jats:p>","DOI":"10.1002\/eji.201545802","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T15:48:32Z","timestamp":1462808912000},"page":"1997-2007","source":"Crossref","is-referenced-by-count":9,"title":["Activation\u2010dependent cell death of human monocytes is a novel mechanism of fine\u2010tuning inflammation and autoimmunity"],"prefix":"10.1002","volume":"46","author":[{"given":"Jan","family":"D\u00e4britz","sequence":"first","affiliation":[{"name":"Department of Pediatric Rheumatology and Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"},{"name":"Department of Pediatrics University Hospital Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toni","family":"Weinhage","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology and Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Varga","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology and Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Wirth","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology and Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Ehrchen","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Barczyk\u2010Kahlert","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Roth","sequence":"additional","affiliation":[{"name":"Institute of Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Schwarz","sequence":"additional","affiliation":[{"name":"St. Josef\u2010Stift  Sendenhorst Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Foell","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology and Immunology University Hospital M\u00fcnster  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00129"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2027"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2044"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2031"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23291"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38647"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.11.30"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-201703"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101751"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2115"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2011.11.015"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.4049\/jimmunol.141.5.1516","article-title":"Synergistic activation of human monocytes by granulocyte\u2010macrophage colony\u2010stimulating factor and IFN\u2010gamma. 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