{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:08:26Z","timestamp":1791637706627,"version":"4.3.4"},"reference-count":63,"publisher":"American Society for Clinical Investigation","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,5,18]]},"abstract":"<jats:p>\n                    Many effector mechanisms of neutrophils have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Neutrophil extracellular traps (NETs) have been assigned a particularly detrimental role. Here we investigated the functional impact of neutrophils and NETs on a mouse model of lupus triggered by intraperitoneal injection of the cell death\u2013inducing alkane pristane. Pristane-induced lupus (PIL) was aggravated in 2 mouse strains with impaired induction of NET formation, i.e., NOX2-deficient (\n                    <jats:italic>Ncf1<\/jats:italic>\n                    -mutated) and peptidyl arginine deiminase 4\u2013deficient (PAD4-deficient) mice, as seen from elevated levels of antinuclear autoantibodies (ANAs) and exacerbated glomerulonephritis. We observed a dramatically reduced ability to form pristane-induced NETs in vivo in both\n                    <jats:italic>Ncf1<\/jats:italic>\n                    -mutated and PAD4-deficient mice, accompanied by higher levels of inflammatory mediators in the peritoneum. Similarly, neutropenic Mcl-1\n                    <jats:sup>\u0394Myelo<\/jats:sup>\n                    mice exhibited higher levels of ANAs, which indicates a regulatory function in lupus of NETs and neutrophils. Blood neutrophils from\n                    <jats:italic>Ncf1<\/jats:italic>\n                    -mutated and human individuals with SLE exhibited exuberant spontaneous NET formation. Treatment with specific chemical NOX2 activators induced NET formation and ameliorated PIL. Our findings suggest that aberrant NET is one of the factors promoting experimental lupus-like autoimmunity by uncontrolled release of inflammatory mediators.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.92920","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T11:00:52Z","timestamp":1495018852000},"source":"Crossref","is-referenced-by-count":135,"title":["Experimental lupus is aggravated in mouse strains with impaired induction of neutrophil extracellular traps"],"prefix":"10.1172","volume":"2","author":[{"given":"Deborah","family":"Kienh\u00f6fer","sequence":"first","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Hahn","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5656-8653","authenticated-orcid":true,"given":"Julia","family":"Stoof","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janka Zs\u00f3fia","family":"Csepregi","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 1 \u2013 Gastroenterology, Pneumology and Endocrinology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Reinwald","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilma","family":"Urbonaviciute","sequence":"additional","affiliation":[{"name":"Section of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Johnsson","sequence":"additional","affiliation":[{"name":"Redoxis AB, Medicon Village Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Mauer\u00f6der","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata J.","family":"Podolska","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona H.","family":"Biermann","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Leppkes","sequence":"additional","affiliation":[{"name":"Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Harrer","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Hultqvist","sequence":"additional","affiliation":[{"name":"Redoxis AB, Medicon Village Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4849-8541","authenticated-orcid":true,"given":"Peter","family":"Olofsson","sequence":"additional","affiliation":[{"name":"ProNoxis AB, Medicon Village Lund, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Munoz","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-1157","authenticated-orcid":true,"given":"Attila","family":"Mocsai","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 1 \u2013 Gastroenterology, Pneumology and Endocrinology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Schett","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 1 \u2013 Gastroenterology, Pneumology and Endocrinology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus H.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Friedrich-Alexander-University Erlangen-N\u00fcrnberg (FAU), Department of Internal Medicine 3 \u2013 Rheumatology and Immunology, Universit\u00e4tsklinikum Erlangen, Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2017,5,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0337679100"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104549"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115474"},{"issue":"73","key":"B5","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001180","article-title":"Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus","volume":"3","author":"Lande","year":"2011","journal-title":"Sci Transl Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909927107"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200606027"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100239"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5828"},{"issue":"157","key":"B10","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3004801","article-title":"NADPH oxidase inhibits the pathogenesis of systemic lupus erythematosus","volume":"4","author":"Campbell","year":"2012","journal-title":"Sci Transl Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113251108"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.07.050"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.6.2341"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050125"},{"issue":"9","key":"B15","doi-asserted-by":"crossref","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheum"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.06.003"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2000.01276.x"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.09.009"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.10934"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem117"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2010.05.001"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4777"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3109\/08916934.2012.719948"},{"key":"B24","article-title":"Cluster of systemic lupus erythematosus (SLE) associated with an oil field waste site: a cross sectional study","volume":"6","author":"Dahlgren","year":"2007","journal-title":"Environ Health"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-03-013771"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00178.x"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.7.5101"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200806072"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2013.00038","article-title":"Opposition between PKC isoforms regulates histone deimination and neutrophil extracellular chromatin release","volume":"4","author":"Neeli","year":"2013","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3547"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103551"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100450"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021553"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-013-0375-7"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4027"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780251101"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/ar4575"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000197"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67390"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00435.2010"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303312"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1021\/jm301755q"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-004-0679-8"},{"issue":"1","key":"B44","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1058","article-title":"Positional identification of Ncf1 as a gene that regulates arthritis severity in rats","volume":"33","author":"Olofsson","year":"2003","journal-title":"Nat Genet"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403831101"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405798111"},{"issue":"1\u20132","key":"B47","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jneuroim.2007.09.020","article-title":"Oxygen radical production and severity of the Guillain--Barr\u00e9 syndrome","volume":"192","author":"Mossberg","year":"2007","journal-title":"J Neuroimmunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63509-2"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00054.2014"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.1.305"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/art.37914"},{"issue":"1","key":"B52","doi-asserted-by":"crossref","first-page":"71","DOI":"10.5858\/2000-124-0071-GFCUOT","article-title":"Guidelines for clinical use of the antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists","volume":"124","author":"Kavanaugh","year":"2000","journal-title":"Arch Pathol Lab Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2003.08.034"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1080\/08916930400022715"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12378"},{"key":"B56","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2016.00328","article-title":"NETosis - does it really represent nature\u2019s \u201csuicide bomber\u201d?","volume":"7","author":"Yousefi","year":"2016","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2016.00461","article-title":"A critical reappraisal of neutrophil extracellular traps and NETosis mimics based on differential requirements for protein citrullination","volume":"7","author":"Konig","year":"2016","journal-title":"Front Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-457671"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5788"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4217"},{"issue":"2","key":"B61","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/jlb.67.2.210","article-title":"P47(phox)-deficient NADPH oxidase defect in neutrophils of diabetic mouse strains, C57BL\/6J-m db\/db and db\/+","volume":"67","author":"Huang","year":"2000","journal-title":"J Leukoc Biol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1211588"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(95)02189-2"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/92920\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:37:17Z","timestamp":1779197837000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/92920"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,18]]},"references-count":63,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,5,18]]},"published-print":{"date-parts":[[2017,5,18]]}},"alternative-id":["10.1172\/jci.insight.92920"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.92920","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,18]]},"article-number":"e92920"}}