{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:54:32Z","timestamp":1787662472816,"version":"build-2736575974"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["Intramural"],"award-info":[{"award-number":["Intramural"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,8]]},"abstract":"<jats:p>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs are potent immunosuppressive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells that are critical to maintain immune quiescence and prevent autoimmunity. Both the generation and maintenance of Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs depend on the cytokine IL-2. Hence, the expression of the IL-2 receptor\n                    <jats:bold>\u03b1<\/jats:bold>\n                    -chain (CD25) is not only considered a specific marker, but also a nonredundant requirement for Tregs. Here, we report that Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs in the small intestine (SI) epithelium, a critical barrier tissue, are exempt from such an IL-2 requirement, since they had dramatically downregulated CD25 expression, showed minimal STAT5 phosphorylation ex vivo, and were unable to respond to IL-2 in vitro. Nonetheless, SI epithelial Tregs survived and were present at the same frequency as in other lymphoid organs, and they retained potent suppressor function that was associated with high levels of CTLA-4 expression and the production of copious amounts of IL-10. Moreover, adoptive transfer experiments of Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs revealed that such IL-2\u2013independent survival and effector functions were imposed by the SI epithelial tissue, suggesting that tissue adaptation is a mechanism that tailors the effector function and survival requirements of Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    Tregs specific to the tissue environment.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.149656","type":"journal-article","created":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T14:00:55Z","timestamp":1636293655000},"source":"Crossref","is-referenced-by-count":17,"title":["The small intestine epithelium exempts Foxp3+ Tregs from their IL-2 requirement for homeostasis and effector function"],"prefix":"10.1172","volume":"6","author":[{"given":"Praveen","family":"Prakhar","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaylene","family":"Alvarez-DelValle","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6510-5685","authenticated-orcid":true,"given":"Hilary","family":"Keller","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA."},{"name":"Department of Surgery, Guthrie Robert Packer Hospital, Sayre, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5746-0073","authenticated-orcid":true,"given":"Assiatu","family":"Crossman","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Tai","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoo Kyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medical Nutrition-AgeTech-Service Convergence Major, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9547-9055","authenticated-orcid":true,"given":"Jung-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1178"},{"issue":"9","key":"B2","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a007021","article-title":"Treg cells, life history, and diversity","volume":"4","author":"Benoist","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.002"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.26.021607.090357"},{"issue":"3","key":"B5","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). 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