{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:06:27Z","timestamp":1791270387884,"version":"4.1.0"},"reference-count":190,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Regulatory T cell (Treg) therapy has emerged as a promising strategy to control pathological immune responses in autoimmunity, graft-versus-host disease, and solid organ transplantation. Most clinical studies to date have relied on autologous Tregs expanded ex vivo, an approach that has demonstrated safety and feasibility but remains limited by variable cell quality, restricted scalability, and complex manufacturing requirements. To address these constraints, multiple alternative strategies are being developed, including the induction of regulatory phenotypes in conventional T cells, the engineering of antigen-specific Tregs, and the generation of allogeneic \u201coff-the-shelf\u201d regulatory cell products. In parallel, induced pluripotent stem cells (iPSCs) offer a renewable and standardized source for regulatory T cell generation, enabling extensive genetic engineering and batch consistency. Early-phase clinical trials with CD4\n                    <jats:sup>+<\/jats:sup>\n                    Tregs have established an excellent safety profile, and initial clinical evaluation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    Tregs is now underway. This review provides a comprehensive and comparative analysis of the biological principles, engineering strategies, and translational challenges that shape the development of regulatory T cell-based immunotherapies.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1797186","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:22:26Z","timestamp":1776403346000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Charleen","family":"Plaisse","sequence":"first","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale (INSERM), Center for Research in Transplantation and Translational Immunology, UMR 1064, ITUN","place":["Nantes, 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