{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:53Z","timestamp":1787026613089,"version":"build-2736575974"},"reference-count":176,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"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                    The long-term outcomes of solid organ transplantation are constrained by alloimmune rejection and the toxicities of lifelong immunosuppression; durable tolerance therefore remains an unmet goal. Regulatory T cells are central mediators of peripheral tolerance, capable of restraining cellular and antibody-mediated rejection while shaping the intragraft inflammatory and repair milieu, supporting a mechanistic rationale for immunosuppression minimization. This review integrates key mechanisms by which Tregs regulate transplant immunity and summarizes evidence for Treg-directed interventions from preclinical studies to early clinical translation across liver, kidney, heart, and lung transplantation. To address the persistent gap between biological promise and inconsistent clinical efficacy, we organize translational barriers using a failure-mode perspective across the therapeutic continuum, encompassing product attributes and manufacturing quality,\n                    <jats:italic>in vivo<\/jats:italic>\n                    delivery and persistence, phenotypic stability under inflammatory stress, target engagement, and endpoint sensitivity. In addition, we outline a biomarker-driven evaluation approach centered on quantifiable proof-of-biology and clinically meaningful surrogate endpoints to enable patient stratification, dose\/regimen optimization, and risk-controlled immunosuppression minimization. Together, advances in precision engineering, harmonized CMC standards, and mechanism-linked immune monitoring may facilitate reproducible and verifiable tolerance-oriented immunotherapies in solid organ transplantation.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1823841","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T04:51:55Z","timestamp":1778129515000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Regulatory T cell therapy in solid organ transplantation: mechanisms, translational progress, and remaining barriers"],"prefix":"10.3389","volume":"17","author":[{"given":"Jie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xusheng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangli","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Union 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