{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:24:25Z","timestamp":1788355465580,"version":"build-2803163510"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"First Affiliated Hospital, Sun Yat-sen University","award":["2022M723604"],"award-info":[{"award-number":["2022M723604"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In this study, we investigate the mechanisms by which ischemia-free liver transplantation (IFLT) mitigates ischemia-reperfusion injury (IRI) and identify key therapeutic targets. Clinical data from 200 patients were collected to evaluate perioperative recovery and overall outcomes. Liver tissues were obtained from donors at the preprocurement, end-of-preservation, and postperfusion stages. Gene expression profiles were examined using single-cell transcriptomic analysis. Phenotypic and functional characteristics were evaluated using flow cytometry, and protein expression was assessed using immunofluorescence, immunohistochemistry, and enzyme-linked immunosorbent assay. Animal models of IRI were employed to examine the effects of HIF-2\u03b1 inhibition in vivo. PT-2385 was administered to inhibit HIF-2\u03b1, and 100\u2009\u00b5g of anti-mouse CD8\u03b1 monoclonal antibody was injected to deplete CD8+ T cells. Patients in the IFLT group exhibited a lower incidence of early allograft dysfunction and a higher 1-yr survival rate. Differential gene expression analysis of IRI-related genes in 14 paired liver samples from conventional liver transplantation revealed significant upregulation of HIF-2\u03b1 in postreperfusion tissues, predominantly expressed in CD69+CD103\u2212CD8+ T cells. The up-regulated genes were enriched in TNF-related signaling pathways. Inhibition of HIF-2\u03b1 reduced the number of CD69+CD103\u2212CD8+ T cells and alleviated liver injury in vivo. In IFLT, genes in this pathway were not significantly upregulated. Under HIF-2\u03b1 stimulation, CD69+CD103\u2212CD8+ T cells exacerbate organ and tissue injury through TNF-related signaling. In IFLT, the absence of significant pathway upregulation suggests effective prevention of IRI.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag005","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:32:44Z","timestamp":1776832364000},"source":"Crossref","is-referenced-by-count":1,"title":["Ischemia-free liver transplantation alleviates liver transplant injury caused by CD69+CD103\u2212CD8+T cells by regulating HIF-2\u03b1 expression"],"prefix":"10.1093","volume":"215","author":[{"given":"Zhitao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangzhou Medical University , Guangzhou,","place":["China"]},{"name":"Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University , Guangzhou,","place":["P.R. China"]},{"name":"Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology , Guangzhou,","place":["China"]},{"name":"Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation) , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Ji","sequence":"additional","affiliation":[{"name":"Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University , Guangzhou,","place":["P.R. 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China"]},{"name":"Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology , Guangzhou,","place":["China"]},{"name":"Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation) , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqian","family":"Zhong","sequence":"additional","affiliation":[{"name":"Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University , Guangzhou,","place":["P.R. China"]},{"name":"Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology , Guangzhou,","place":["China"]},{"name":"Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation) , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"He","sequence":"additional","affiliation":[{"name":"Organ Transplant Center, First Affiliated Hospital of Sun Yat-sen University , Guangzhou,","place":["P.R. 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