{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:09:40Z","timestamp":1787018980033,"version":"build-2736575974"},"reference-count":40,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province, China","doi-asserted-by":"publisher","award":["2021JJ31018"],"award-info":[{"award-number":["2021JJ31018"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Innovation Foundation of Hunan Province","award":["2020SK53614"],"award-info":[{"award-number":["2020SK53614"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"crossref","award":["2019YFA0110703"],"award-info":[{"award-number":["2019YFA0110703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272102"],"award-info":[{"award-number":["82272102"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province, China","doi-asserted-by":"publisher","award":["2020JJ4841"],"award-info":[{"award-number":["2020JJ4841"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971721"],"award-info":[{"award-number":["81971721"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n                    Clinically, xenotransplantation often leads to T-cell-mediated graft rejection. Immunosuppressive agents including polyclonal regulatory T cells (poly-Tregs) promote global immunosuppression, resulting in serious infections and malignancies in patients. Xenoantigen-expanded Tregs (xeno-Tregs) have become a promising immune therapy strategy to protect xenografts with fewer side effects. In this study, we aimed to identify an efficient and stable subset of xeno-Tregs. We enriched CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs using cell sorting and evaluated their suppressive functions and stability in vitro via mixed lymphocyte reaction (MLR), real-time polymerase chain reaction, inflammatory induction assay, and Western blotting. A STAT5 inhibitor was used to investigate the relationship between the function and stability of CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs and the JAK3\u2013STAT5 signaling pathway. A humanized xenotransplanted mouse model was used to evaluate the function of CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs in vivo. Our results show that CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs express higher levels of Foxp3, cytotoxic T-lymphocyte antigen-4 (CTLA4), and Helios and lower levels of interleukin-17 (IL-17) than their CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    counterparts. In addition, CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs showed enhanced suppressive function in xeno-MLR at ratios of 1:4 and 1:16 of Tregs:responder cells. Under inflammatory conditions, a lower percentage of CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs secretes IL-17 and interferon-\u03b3 (IFN-\u03b3). CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs demonstrated an upregulated JAK3\u2013STAT5 pathway compared with that of CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    xeno-Tregs and showed decreased Foxp3, Helios, and CTLA4 expression after addition of STAT5 inhibitor. Mice that received porcine skin grafts showed a normal tissue phenotype and less leukocyte infiltration after reconstitution with CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs. Taken together, these data indicate that CD27\n                    <jats:sup>+<\/jats:sup>\n                    xeno-Tregs may suppress immune responses in a xenoantigen-specific manner, which might be related to the activation of the JAK3\u2013STAT5 signaling pathway.\n                  <\/jats:p>","DOI":"10.1177\/09636897221149444","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T04:02:43Z","timestamp":1673841763000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["CD27-Expressing Xenoantigen-Expanded Human Regulatory T Cells Are Efficient in Suppressing Xenogeneic Immune Response"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3602-0340","authenticated-orcid":false,"given":"Lu","family":"Cao","sequence":"first","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"},{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-9927","authenticated-orcid":false,"given":"Xiaoqian","family":"Ma","sequence":"additional","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"},{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"},{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"},{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cejun","family":"Yang","sequence":"additional","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"},{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang","family":"Li","sequence":"additional","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3409-7846","authenticated-orcid":false,"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Institute for Cell Transplantation and Gene Therapy, The Third XiangYa Hospital, Central South University, Changsha, China"},{"name":"Department of Radiology, The Third XiangYa Hospital, Central South University, Changsha, 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