{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:13:20Z","timestamp":1788416000782,"version":"build-2803163510"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K21768"],"award-info":[{"award-number":["25K21768"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001695","name":"Japan Science and Technology Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Regulatory T (Treg) cells are a specialized subset of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells indispensable for the establishment and maintenance of immunological tolerance. Treg cells employ diverse mechanisms of immune regulation mediated by a broad repertoire of immunosuppressive molecules under the control of the lineage-specifying transcription factor FoxP3. Functional defects in Treg cells disrupt immune homeostasis and are implicated in the pathogenesis of autoimmune diseases, chronic inflammatory disorders, and cancer. In this article, we revisit three decades of progress since Sakaguchi\u2019s seminal discovery of CD25\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells in 1995, highlighting the physiological significance of dominant immune tolerance and its underlying molecular mechanisms. We then discuss how these mechanisms have inspired therapeutic strategies aimed at enhancing or harnessing Treg cell function, the remaining challenges and recent technological advances toward clinical translation, and the near-future prospects for Treg-based therapies in immune-mediated diseases.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1925870","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:21:55Z","timestamp":1788412915000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Thirty years in, regulatory T cells are ready for medicine"],"prefix":"10.3389","volume":"17","author":[{"given":"Ryoji","family":"Kawakami","sequence":"first","affiliation":[{"name":"Experimental Pathology Lab, Institute for Life and Medical Sciences, Kyoto University","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayush","family":"Jain","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Universit\u00e4tsklinikum Carl Gustav Carus, Technische Universit\u00e4t Dresden","place":["Dresden, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.2.302","article-title":"Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo","volume":"165","author":"Jenkins","year":"1987","journal-title":"J Exp Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90568-x","article-title":"T cell tolerance by clonal elimination in the thymus","volume":"49","author":"Kappler","year":"1987","journal-title":"Cell"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1972593","article-title":"Clonal deletion versus clonal anergy: the role of the thymus in inducing self tolerance","volume":"248","author":"Ramsdell","year":"1990","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","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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