{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:17:35Z","timestamp":1790727455896,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Takeda Pharmaceuticals","award":["ISR-2014-1000892"],"award-info":[{"award-number":["ISR-2014-1000892"]}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK09907"],"award-info":[{"award-number":["R01DK09907"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Micky & Madeleine Arison Family Foundation Crohn's & Colitis Discovery Laboratory"},{"name":"The Martin Kalser Chair in Gastroenterology"},{"DOI":"10.13039\/100006686","name":"University of Miami","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006686","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["R01AI118931"],"award-info":[{"award-number":["R01AI118931"]}]},{"name":"Senior Research","award":["422515"],"award-info":[{"award-number":["422515"]}]},{"DOI":"10.13039\/100011684","name":"Crohn\u2019s & Colitis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Inflammatory bowel disease (IBD) involves chronic T cell\u2013mediated inflammatory responses. Vedolizumab (VDZ), a monoclonal antibody against \u03b14\u03b27 integrin, inhibits lymphocyte extravasation into intestinal mucosae and is effective in ulcerative colitis (UC) and Crohn\u2019s disease (CD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>We sought to identify immune cell phenotypic and gene expression signatures that related to response to VDZ.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Peripheral blood (PBMC) and lamina propria mononuclear cells (LPMCs) were analyzed by flow cytometry and Cytofkit. Sorted CD4\u2005+\u2005memory (Tmem) or regulatory T (Treg) cells from PBMC and LPMC were analyzed by RNA sequencing (RNA-seq). Clinical response (\u22652-point drop in partial Mayo scores [UC] or Harvey-Bradshaw index [CD]) was assessed 14 to 22 weeks after VDZ initiation. Machine-learning models were used to infer combinatorial traits that predicted response to VDZ.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventy-one patients were enrolled: 37 received VDZ and 21 patients remained on VDZ\u2005&amp;gt;2 years. Fourteen of 37 patients (38%; 8 UC, 6 CD) responded to VDZ. Immune cell phenotypes and CD4\u2005+\u2005Tmem and Treg transcriptional behaviors were most divergent between the ileum and colon, irrespective of IBD subtype or inflammation status. Vedolizumab treatment had the greatest impact on Treg metabolic pathways, and response was associated with increased expression of genes involved in oxidative phosphorylation. The strongest clinical predictor of VDZ efficacy was concurrent use of thiopurines. Mucosal tissues offered the greatest number of response-predictive biomarkers, whereas PBMC Treg-expressed genes were the best predictors in combinatorial models of response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mucosal and peripheral blood immune cell phenotypes and transcriptional profiles can inform VDZ efficacy and inform new opportunities for combination therapies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izac151","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T11:58:21Z","timestamp":1661169501000},"page":"1800-1812","source":"Crossref","is-referenced-by-count":25,"title":["Transcriptional Behavior of Regulatory T Cells Predicts IBD Patient Responses to Vedolizumab Therapy"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-0574","authenticated-orcid":false,"given":"Maria 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Diaz","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine D","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , Jupiter, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Venables","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Scripps Research Institute , Jupiter, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Reich","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, The Scripps Research Institute , Jupiter, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gogce","family":"Crynen","sequence":"additional","affiliation":[{"name":"Center for Computational Biology and Bioinformatics, The Scripps Research Institute , Jupiter, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amar R","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Kerman","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana M","family":"Damas","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Santander","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Pignac-Kobinger","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Miami Miller School of Medicine , Miami, Florida , 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