{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:32:38Z","timestamp":1790821958740,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"18","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants & Redox Signaling"],"published-print":{"date-parts":[[2017,12]]},"abstract":"\n Aims:<\/jats:title>\n \n Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the\n Ncf1<\/jats:italic>\n gene is associated with increased arthritis severity. In this study, we generated targeted\n Ncf1<\/jats:italic>\n knock-in mice with inducible\n Ncf1<\/jats:italic>\n expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Targeted\n Ncf1<\/jats:italic>\n knock-in mice lacked NOX2-derived ROS, and\n in vivo<\/jats:italic>\n allelic conversion of\n Ncf1<\/jats:italic>\n by the\n \n CreER\n T2<\/jats:sup>\n <\/jats:italic>\n recombinase led to full protein expression and ROS production within 10 days. Mice in which\n Ncf1<\/jats:italic>\n had been activated before immunization with type II collagen (CII) developed only mild clinical symptoms of collagen-induced arthritis (CIA), whereas the ROS-deficient littermates had severe arthritis. The functional\n Ncf1<\/jats:italic>\n restricted the expansion of IL-17A-producing T cells specific for the immunodominant CII peptide. When the\n Ncf1<\/jats:italic>\n gene was activated after the priming phase,\n Ncf1<\/jats:italic>\n -dependent protection from autoimmune arthritis was still observed, together with a reduced number of splenic monocytes but it was not associated with alterations in peptide-specific T cell response. The\n Ncf1<\/jats:italic>\n -deficient mice expressed pronounced interferon signature, which could be normalized by conditional expression of\n Ncf1<\/jats:italic>\n and was also present in the\n Ncf1<\/jats:italic>\n -mutated mouse during arthritis.\n <\/jats:p>\n <\/jats:sec>\n \n Innovation and Conclusion:<\/jats:title>\n \n Ncf1<\/jats:italic>\n deficiency has been known to predispose to autoimmunity in both humans and rodents. Our\n in vivo<\/jats:italic>\n results point to a regulatory role of NOX2-derived ROS not only during priming but also during the effector phase of CIA, most likely\n via<\/jats:italic>\n different mechanisms.\n Antioxid. Redox Signal<\/jats:italic>\n . 27, 1473\u20131490.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/ars.2016.6981","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T15:00:30Z","timestamp":1493823630000},"page":"1473-1490","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":27,"title":["Reactive Oxygen Species Regulate Both Priming and Established Arthritis, but with Different Mechanisms"],"prefix":"10.1177","volume":"27","author":[{"given":"Outi","family":"Sareila","sequence":"first","affiliation":[{"name":"University of Turku","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Hagert","sequence":"additional","affiliation":[{"name":"University of Turku","place":["Finland"]},{"name":"The National Doctoral Programme, Informational and Structural Biology, Turku, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiina","family":"Kelkka","sequence":"additional","affiliation":[{"name":"University of Turku","place":["Finland"]},{"name":"Turku Doctoral Programme of Biomedical Sciences, Turku, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjo","family":"Linja","sequence":"additional","affiliation":[{"name":"University of Turku","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingze","family":"Xu","sequence":"additional","affiliation":[{"name":"Karolinska Institutet","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kihlberg","sequence":"additional","affiliation":[{"name":"Uppsala University","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"University of Turku","place":["Finland"]},{"name":"Karolinska Institutet","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.080074897"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.639021"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200212)32:12<3776::AID-IMMU3776>3.0.CO;2-A"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.021"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03321.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.3806"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.08.003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.4A0314-139R"},{"key":"e_1_3_3_10_2","first-page":"6","article-title":"Physiological evidence for diversification of IFNalpha- and IFNbeta-mediated response programs in different autoimmune diseases","author":"de Jong TD","year":"2016","unstructured":"de Jong TD, , Vosslamber S, , Mantel E, , de Ridder S, , Wesseling JG, , van der Pouw Kraan TC, , Leurs C, , Hegen H, , Deisenhammer F, , Killestein J, , Lundberg IE, , Vencovsky J, , Nurmohamed MT, , van Schaardenburg D, , Bultink IE, , Voskuyl AE, , Pegtel DM, , van der Laken CJ, , Bijlsma JW, , and Verweij CL. Physiological evidence for diversification of IFNalpha- and IFNbeta-mediated response programs in different autoimmune diseases. 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