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Herein, we show that the human cathelicidin derived antimicrobial peptide LL37 associates with and directs plasma extracellular vesicles (EV) to immune cells, thereby leading to enhanced immune activation aggravating BD pathology. Notably, disease activity was correlated with elevated levels of circulating LL37 and EV plasma concentration. Stimulation of healthy PBMC with active BD patient EVs induced heightened IL1\u03b2, IFN\u03b1, IL6 and IP10\u00a0secretion compared to healthy and inactive BD EVs. Remarkably, when mixed with LL37, healthy plasma\u2010EVs triggered a robust immune activation replicating the pathology inducing properties of BD EVs. The findings of this study could be of clinical interest in the management of BD, implicating LL37\/EV association as one of the major contributors of BD pathogenesis.<\/jats:p><jats:p><jats:bold>Abbreviations<\/jats:bold>: BD: Beh\u00e7et's disease; EV: extracellular vesicle; BB: binding buffer; AnV: annexin V; autologEV: autologous extracellular vesicles; alloEV: allogeneic extracellular vesicles<\/jats:p>","DOI":"10.1080\/20013078.2017.1284449","type":"journal-article","created":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T23:48:46Z","timestamp":1518047326000},"update-policy":"https:\/\/doi.org\/10.1080\/tandf_crossmark_01","source":"Crossref","is-referenced-by-count":14,"title":["Circulating LL37 targets plasma extracellular vesicles to immune cells and intensifies Beh\u00e7et's disease severity"],"prefix":"10.1002","volume":"6","author":[{"given":"Tamer","family":"Kahraman","sequence":"first","affiliation":[{"name":"Science Faculty Department of Molecular Biology and Genetics Bilkent University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gozde","family":"Gucluler","sequence":"additional","affiliation":[{"name":"Science Faculty Department of Molecular Biology and Genetics Bilkent University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Simsek","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Gulhane School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuat Cem","family":"Yagci","sequence":"additional","affiliation":[{"name":"Science Faculty Department of Molecular Biology and Genetics Bilkent University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzaffer","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Science Faculty Department of Molecular Biology and Genetics Bilkent University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Ozen","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Middle East Technical University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayhan","family":"Dinc","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Gulhane School of Medicine Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayda","family":"Gursel","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Middle East Technical University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lolai","family":"Ikromzoda","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center Sabanci University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga","family":"Sutlu","sequence":"additional","affiliation":[{"name":"Nanotechnology Research and Application Center Sabanci University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Gay","sequence":"additional","affiliation":[{"name":"Department of Rheumatology University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihsan","family":"Gursel","sequence":"additional","affiliation":[{"name":"Science Faculty Department of Molecular Biology and Genetics Bilkent University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.autrev.2014.01.056","article-title":"Biotherapies in Behcet's disease","volume":"13","author":"Comarmond C","year":"2014","journal-title":"Autoimmun Rev"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.131249"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel329"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-013-1036-5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-010-0132-z"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/030097402320318387"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2013.02.010"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.9.6415"},{"key":"e_1_2_8_10_1","first-page":"329","article-title":"Divergent cytokine production profile in Behcet's disease. 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