{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:33:28Z","timestamp":1791725608467,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1213,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["093885\/Z\/10\/Z"],"award-info":[{"award-number":["093885\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012295","name":"NIHR | NIHR Newcastle Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012295","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Targeting interactions between \u03b14\u03b27 integrin and endothelial adhesion molecule MAdCAM-1 to inhibit lymphocyte migration to the gastrointestinal tract is an effective therapy in inflammatory bowel disease (IBD). Following lymphocyte entry into the mucosa, a subset of these cells expresses \u03b1E\u03b27 integrin, which is expressed on proinflammatory lymphocytes, to increase cell retention. The factors governing lymphocyte migration into the intestinal mucosa and \u03b1E integrin expression in healthy subjects and IBD patients remain incompletely understood. We evaluated changes in factors involved in lymphocyte migration and differentiation within tissues. Both ileal and colonic tissue from active IBD patients showed upregulation of ICAM-1, VCAM-1, and MAdCAM-1 at the gene and protein levels compared with healthy subjects and\/or inactive IBD patients. \u03b21 and \u03b27 integrin expression on circulating lymphocytes was similar across groups. TGF-\u03b21 treatment induced expression of \u03b1E on both \u03b27+ and \u03b27\u2212 T cells, suggesting that cells entering the mucosa independently of MAdCAM-1\/\u03b14\u03b27 can become \u03b1E\u03b27+. ITGAE gene polymorphisms did not alter protein induction following TGF-\u03b21 stimulation. Increased phospho-SMAD3, which is directly downstream of TGF-\u03b2, and increased TGF-\u03b2\u2013responsive gene expression were observed in the colonic mucosa of IBD patients. Finally, in vitro stimulation experiments showed that baseline \u03b27 expression had little effect on cytokine, chemokine, transcription factor, and effector molecule gene expression in \u03b1E+ and \u03b1E\u2212 T cells. These findings suggest cell migration to the gut mucosa may be altered in IBD and \u03b14\u03b27\u2212, and \u03b14\u03b27+ T cells may upregulate \u03b1E\u03b27 in response to TGF-\u03b2 once within the gut mucosa.<\/jats:p>","DOI":"10.4049\/jimmunol.2100220","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T17:10:26Z","timestamp":1632503426000},"page":"2245-2254","source":"Crossref","is-referenced-by-count":78,"title":["Regulation and Role of \u03b1E Integrin and Gut Homing Integrins in Migration and Retention of Intestinal Lymphocytes during Inflammatory Bowel Disease"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0637-4092","authenticated-orcid":false,"given":"Mary E","family":"Keir","sequence":"first","affiliation":[{"name":"Genentech Inc. , South San Francisco, 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