{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:06:42Z","timestamp":1773194802394,"version":"3.50.1"},"reference-count":25,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union\u2019s Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie","doi-asserted-by":"publisher","award":["847551"],"award-info":[{"award-number":["847551"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005302","name":"Onassis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005302","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NWO ZonMW VENI","award":["09150161810112"],"award-info":[{"award-number":["09150161810112"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Etrasimod is an oral selective sphingosine-1 phosphate receptor modulator, and its anti-inflammatory mechanism of action in inflammatory bowel diseases is not completely understood. It targets pro-inflammatory immune cells expressing sphingosine-1-phosphate receptors during their migration from the lymphatic system to the circulation and intestinal mucosa. Reductions in certain lymphocyte subsets in the peripheral blood have been reported, but its effects in lymph nodes remain unknown. This study investigated changes in leukocyte subpopulations in peripheral lymph nodes and blood in Crohn\u2019s disease patients treated with etrasimod. Moderate-to-severe Crohn\u2019s disease patients participated in this randomized, double-blind study, within the phase 2 CULTIVATE clinical trial. At baseline and after 14 weeks of etrasimod treatment, peripheral blood and inguinal lymph node biopsies were obtained. Isolated peripheral blood mononuclear cells and lymph node leukocyte populations were analyzed at single cell level using mass cytometry at both timepoints. The immunophenotyping revealed 15 innate and adaptive major immune cell populations, as well as 14 subpopulations of CD4+ and CD8+ T-cells. In peripheral lymph nodes, etrasimod resulted in significant accumulation of na\u00efve, central memory, and effector memory CD4+ T-cells (+10.7%, +4.2%, and +2.3%, respectively; all p = 0.03), as well as na\u00efve CD8+ T-cells (+4.2%; p = 0.03). Conversely, these subsets were reduced in peripheral blood (\u22126.2%, \u22126.0%, \u22122.0%, and \u22122.2%, respectively; all p = 0.03). Na\u00efve and memory B-cells decreased in the circulation (\u22121.7%, p = 0.057; \u22120.6%, p = 0.03, respectively) but were unchanged in the lymph nodes. Innate immune cell populations remained mostly unaffected in both compartments. Our data indicate that etrasimod\u2019s pharmacodynamic effect is related primarily with the attenuation of the T-cell mediated inflammation with minor changes in B-cells. However, additional follow-up studies are needed for the validation of these observations in the context of Crohn\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms27052447","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:25:59Z","timestamp":1772817959000},"page":"2447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Etrasimod Treatment Modulates Circulating and Lymph Node-Derived Lymphocytes in Crohn\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6994-6149","authenticated-orcid":false,"given":"Dimitrios","family":"Nikolakis","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Rheumatology & Clinical Immunology, Amsterdam Rheumatology & Immunology Center (ARC), Amsterdam UMC, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Center for Infectious Medicine (CIM), Department of Medicine Huddinge, Karolinska Institutet, ANA Futura, 141 52 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-8353","authenticated-orcid":false,"given":"Maarten J.","family":"Pruijt","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0648-0642","authenticated-orcid":false,"given":"Jan","family":"Verhoeff","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floris A. E.","family":"de Voogd","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3080-9806","authenticated-orcid":false,"given":"Christoph","family":"Teichert","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rathi D.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Pfizer Inc., South San Francisco, CA 94080, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-6409","authenticated-orcid":false,"given":"Diogo","family":"Branquinho","sequence":"additional","affiliation":[{"name":"Pfizer Inc., New York, NY 10001, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Crosby","sequence":"additional","affiliation":[{"name":"Pfizer Inc., San Diego, CA 92121, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-878X","authenticated-orcid":false,"given":"Marleen G. H.","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Department of Rheumatology & Clinical Immunology, Amsterdam Rheumatology & Immunology Center (ARC), Amsterdam UMC, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joep","family":"Grootjans","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert R.","family":"D\u2019Haens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Gastroenterology Endocrinology & Metabolism Institute, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"Xavier","year":"2007","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3748\/wjg.v20.i1.91","article-title":"Inflammatory bowel disease: Pathogenesis","volume":"20","author":"Zhang","year":"2014","journal-title":"World J. 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