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This study aims to investigate how this procedure impacts local and systemic immunity compared to conventional liver transplantation (CLT). Immunohistochemistry, immunofluorescence staining, single\u2010cell RNA sequencing (scRNA\u2010seq), and multiplex cytokine are used to illustrate distinct local and systemic immunity. In contrast to CLT, IFLT reduces neutrophil infiltration and neutrophil extracellular trap formation in grafts. By constructing an immune cell chimerism atlas, we reveal that IFLT reduces recipient\u2010derived monocyte infiltration by suppressing ANXA1\u2010FPR1 signaling through the STAT3\u2010HIF\u20101\u03b1 pathway, thereby attenuating inflammatory responses in graft monocytes. Additionally, IFLT confers graft protection by upregulating\n                    <jats:italic>HMOX1<\/jats:italic>\n                    expression in monocytes and macrophages. Peripherally, IFLT significantly reduces the expression of MHC II molecules in circulating monocytes. Accordingly, CD8\n                    <jats:sup>+<\/jats:sup>\n                    effector T cell composition, T helper 1 (Th1) and Th17 cytokine levels are reduced, while regulatory T cell (Treg) composition and Th2 cytokine levels are increased in IFLT versus CLT recipients. These results show that IFLT profoundly affects local and systemic immunity in liver transplantation. Recipient\u2010circulating monocytes might play a key role in the interaction between graft IRI and allograft rejection.\n                  <\/jats:p>","DOI":"10.1002\/advs.202502854","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:41:12Z","timestamp":1769517672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Substantially Altered Local and Systemic Immunity in Ischemia\u2010Free Versus Conventional Liver Transplantation"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-9294","authenticated-orcid":false,"given":"Tao","family":"Luo","sequence":"first","affiliation":[{"name":"Organ Transplant Center The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Organ Medicine  Guangzhou China"},{"name":"Guangdong Provincial International Cooperation Base of Science and 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