{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:52:44Z","timestamp":1788306764482,"version":"build-2803163510"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013276","name":"Interreg","doi-asserted-by":"publisher","award":["J22F170001005"],"award-info":[{"award-number":["J22F170001005"]}],"id":[{"id":"10.13039\/100013276","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Vedolizumab (VDZ) is a therapeutic monoclonal antibody approved for the treatment of inflammatory bowel diseases (IBD). VDZ selectively binds to the \u03b14\u03b27 integrin and blocks trafficking of a specific subset of gastrointestinal-homing T-lymphocytes to inflamed tissue. Although VDZ has shown promising results in numerous clinical studies a subgroup of patients do not respond adequately. Mechanistic insights and prognostic biomarkers able to predict which patients might benefit from VDZ therapy are currently lacking. Circulating exosomes were isolated from serum of blood donors and VDZ-treated patients by polymer-based precipitation. The surface expression of \u03b14\u03b27 integrin was evaluated by flow cytometry and the levels of exosome-bound VDZ were investigated by Promonitor-VDZ ELISA kit. The capacity of exosomes to interfere with the adhesion of VDZ-treated CD4+ T cells was assessed by adhesion assay. In this study, we showed that serum exosomes isolated from both blood donor and ulcerative colitis patients express on their surface the VDZ target \u03b14\u03b27 integrin. We observed an increased exosomal sequestration of VDZ in anti-TNF exposed patients compared to anti- TNF\u03b1 na\u00efve patients, according to a greater expression of \u03b14\u03b27 integrin on vesicles surface. Circulating exosomes could compete for VDZ binding with CD4+ T cells since we found that the amount of VDZ bound to T cells was impaired in the presence of exosomes. In addition, we demonstrated that exosomes bind VDZ, which consequently becomes unable to block MadCAM-1-mediated adhesion of lymphocytes. Circulating exosomes might contribute to drug sequestration, possibly affecting the therapeutic efficacy of VDZ in IBD patients. Our data suggest that previous biologic therapy may have altered the sequestration capacity of circulating exosomes, thus reducing the efficacy of VDZ in patients who failed anti-TNF agents.<\/jats:p>","DOI":"10.1371\/journal.pone.0242342","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T16:08:36Z","timestamp":1605197316000},"page":"e0242342","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Circulating exosomes express \u03b14\u03b27 integrin and compete with CD4+ T cells for the binding to Vedolizumab"],"prefix":"10.1371","volume":"15","author":[{"given":"Rossana","family":"Domenis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-3524","authenticated-orcid":true,"given":"Marco","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-8838","authenticated-orcid":true,"given":"Adriana","family":"Cif\u00f9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Scardino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Curcio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-2841","authenticated-orcid":true,"given":"Martina","family":"Fabris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"pone.0242342.ref001","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1097\/MOG.0000000000000364","article-title":"Etiopathogenesis of inflammatory bowel disease","volume":"33","author":"HSP de Souza","year":"2017","journal-title":"Curr Opin Gastroenterol"},{"key":"pone.0242342.ref002","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/s41385-018-0050-3","article-title":"The current state of the art for biological therapies and new small molecules in inflammatory bowel disease","volume":"11","author":"S Paramsothy","year":"2018","journal-title":"Mucosal Immunol"},{"key":"pone.0242342.ref003","doi-asserted-by":"crossref","first-page":"S633","DOI":"10.1093\/ecco-jcc\/jjy011","article-title":"Past, Present and Future of Therapeutic Interventions Targeting Leukocyte Trafficking in Inflammatory Bowel Disease","volume":"12","author":"J Pan\u00e9s","year":"2018","journal-title":"J Crohn\u2019s Colitis"},{"key":"pone.0242342.ref004","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/ecco-jcc\/jjw092","article-title":"An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab","volume":"10","author":"T Wyant","year":"2016","journal-title":"J Crohn\u2019s Colitis"},{"key":"pone.0242342.ref005","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1215734","article-title":"Vedolizumab as Induction and Maintenance Therapy for Ulcerative Colitis","volume":"369","author":"BG Feagan","year":"2013","journal-title":"N Engl J Med. 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