{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:36:00Z","timestamp":1784345760837,"version":"3.55.0"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800664"],"award-info":[{"award-number":["81800664"]}],"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":[[2021,1,1]]},"abstract":"<jats:p>\n                    Xenotransplantation is a potential solution for the severe shortage of human donor organs and tissues. The generation of humanized animal models attenuates strong innate immune responses, such as complement-mediated hyperacute rejection. However, acute vascular rejection and cell mediated rejection remain primary barriers to xenotransplantation, which limits its clinical application. In this study, we systematically investigated the immunosuppressive effect of LEF using a rat-to-mouse heart xenotransplantation model. SD rat xenogeneic hearts were transplanted into C57BL\/6 mice, and survived 34.5 days after LEF treatment. In contrast, BALB\/c allogeneic hearts were transplanted into C57BL\/6 mice, and survived 31 days after LEF treatment. Compared to normal saline treatment, LEF treatment decreased xenoreactive T cells and CD19\n                    <jats:sup>+<\/jats:sup>\n                    B cells in recipient splenocytes. Most importantly, LEF treatment protected myocardial cells by decreasing xenoreactive T and B cell infiltration, inflammatory gene expression, and IgM deposition in grafts. In vivo assays revealed that LEF treatment eliminated xenoreactive and alloreactive T and B lymphocytes by suppressing the activation of the NF-\u03baB signaling pathway. Taken together, these observations complement the evidence supporting the potential use of LEF in xenotransplantation.\n                  <\/jats:p>","DOI":"10.1177\/09636897211054503","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T01:39:47Z","timestamp":1637717987000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Leflunomide Inhibits rat-to-Mouse Cardiac Xenograft Rejection by Suppressing Adaptive Immune Cell Response and NF-\u03baB Signaling Activation"],"prefix":"10.1177","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9593-5391","authenticated-orcid":false,"given":"Yunhan","family":"Ma","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, China"},{"name":"School of Medicine, Xiamen University, Xiamen, China"},{"name":"Department of Clinical Sciences, Malm\u00f6, Lund University, Malm\u00f6, Sweden"},{"name":"Yunhan Ma and Baiyi Xie contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiyi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Urology Surgery, Ruikang Hospital affiliated to Guangxi University of Chinese Medicine, Nanning, China"},{"name":"Yunhan Ma and Baiyi Xie contributed equally to this work."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Medicine, Xiamen University, Xiamen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Organ and Tissue Regeneration, School of Medicine, Xiamen University, Xiamen, China"},{"name":"School of Medicine, Xiamen University, Xiamen, 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