{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:29:39Z","timestamp":1790504979646,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T00:00:00Z","timestamp":1475625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>Aberrant formation of neutrophil extracellular traps (NETs) is a key feature in rheumatoid arthritis (RA) and plays a pivotal role in disease pathogenesis. However, the mechanism through which NETs shape the autoimmune response in RA remains elusive. In this study, we demonstrate that inhibition of peptidylarginine deiminases activity in collagen\u2010induced arthritis (CIA) mouse model significantly reduces NET formation, attenuates clinical disease activity, and prevents joint destruction. Importantly, peptidylarginine deiminase 4 blocking markedly reduces the frequency of collagen\u2010specific IFN\u2010\u03b3\u2010producing T helper 1 (Th1) cells in the draining lymph nodes of immunized mice. Exposure of dendritic cells (DCs) to CIA\u2010derived NETs induces DC maturation characterized by significant upregulation of costimulatory molecules, as well as elevated secretion of IL\u20106. Moreover, CIA\u2010NET\u2010treated DCs promote the induction of antigen\u2010specific Th1 cells in vitro. Finally, NETs from RA patients show an increased potential to induce the maturation of DCs from healthy individuals, corroborating the findings obtained in CIA mouse model. Collectively, our findings delineate an important role of NETs in the induction and expansion of Th1 pathogenic cells in CIA through maturation of DCs and reveal a novel role of NETs in shaping the RA\u2010autoimmune response that could be exploited therapeutically.<\/jats:p>","DOI":"10.1002\/eji.201646542","type":"journal-article","created":{"date-parts":[[2016,9,2]],"date-time":"2016-09-02T12:27:05Z","timestamp":1472819225000},"page":"2542-2554","source":"Crossref","is-referenced-by-count":89,"title":["Neutrophil extracellular traps exacerbate Th1\u2010mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation"],"prefix":"10.1002","volume":"46","author":[{"given":"Garyfalia","family":"Papadaki","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology  Heraklion Greece"},{"name":"Laboratory of Rheumatology, Autoimmunity and Inflammation, Faculty of Medicine University of Crete  Heraklion Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Kambas","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Hematology Democritus University of Thrace  Alexandroupolis Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiana","family":"Choulaki","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology  Heraklion Greece"},{"name":"Laboratory of Rheumatology, Autoimmunity and Inflammation, Faculty of Medicine University of Crete  Heraklion Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Vlachou","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology  Heraklion Greece"},{"name":"Laboratory of Rheumatology, Autoimmunity and Inflammation, Faculty of Medicine University of Crete  Heraklion Greece"},{"name":"Biomedical Research Foundation Academy of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Drakos","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Crete Medical School  Heraklion Crete Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Bertsias","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology  Heraklion Greece"},{"name":"Laboratory of Rheumatology, Autoimmunity and Inflammation, Faculty of Medicine University of Crete  Heraklion Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Ritis","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Hematology Democritus University of Thrace  Alexandroupolis Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios T.","family":"Boumpas","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology  Heraklion Greece"},{"name":"Biomedical Research Foundation Academy of Athens  Athens Greece"},{"name":"4<sup>th<\/sup> Department of Medicine Attikon University Hospital  Athens Greece"},{"name":"Joint Academic Rheumatology Program National and Kapodestrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Pharmacology University of Massachusetts Medical School  Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panayotis","family":"Verginis","sequence":"additional","affiliation":[{"name":"Biomedical Research Foundation Academy of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prodromos","family":"Sidiropoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Rheumatology, Autoimmunity and Inflammation, Faculty of Medicine University of Crete  Heraklion Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,10,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.019877"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.016808"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.001"},{"key":"e_1_2_7_6_1","first-page":"232","article-title":"Neutrophil migration and production of reactive oxygen species during treatment with a fully human anti\u2010tumor necrosis factor\u2010alpha monoclonal antibody in patients with rheumatoid arthritis","volume":"30","author":"den Broeder A. 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