{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:32:01Z","timestamp":1786357921183,"version":"build-2736575974"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:p>Organ transplantation is the definitive treatment for end-stage organ failure, yet long-term graft survival remains substantially limited by ischemia-reperfusion injury (IRI), allograft rejection, and chronic graft dysfunction. Current immunosuppressive regimens have not fully exploited the metabolic plasticity of macrophages, which are central orchestrators of both innate and adaptive immune responses in transplanted organs. Macrophages display remarkable functional plasticity, classically defined by pro-inflammatory (M1)\/anti-inflammatory (M2) polarization, and this dual capacity renders them uniquely impactful in transplanted organs. Accumulating immunometabolic evidence indicates that this plasticity is governed by dynamic metabolic reprogramming orchestrated by key metabolic nodes: M1 macrophages rely primarily on aerobic glycolysis and secrete proinflammatory cytokines, such as IL-1\u03b2, IL-6, and TNF-\u03b1, whereas M2 macrophages depend on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to sustain anti-inflammatory and tissue-repair programs. For example, pyruvate kinase M2, a key glycolytic enzyme, promotes M1 polarization via glycolytic reprogramming and HIF-1\u03b1-dependent inflammatory gene transcription, whereas the carnitine palmitoyltransferase 1A, a rate-limiting enzyme in FAO, supports M2 polarization through FAO-driven OXPHOS. Core metabolic pathways encompass carbohydrate metabolism-glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway-alongside FAO and amino acid catabolism. These pathways are dynamically modulated by microenvironmental cues, such as hypoxia, lactate, and succinate, and in turn dictate macrophage phenotypic identity and effector function. In this review, we comprehensively review the molecular mechanisms underpinning macrophage metabolic reprogramming, from early IRI and acute rejection to chronic rejection, fibrosis, and post-transplant tumor recurrence, linking metabolism to alloimmunity and oncological risk. Emerging therapeutic strategies target macrophage metabolism, including metabolic enzyme inhibitors such as 2-deoxyglucose, which attenuates chronic lung allograft dysfunction, cell-based therapies, nanoparticles, and gene editing, for example macrophage-specific MEK1\/2 ablation via CRISPR\/Cas9, which reprograms glycolysis to OXPHOS and ameliorates cardiac rejection. Harnessing these metabolic nodes may complement current immunosuppression and improve graft survival, warranting future clinical evaluation.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1868319","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:56:22Z","timestamp":1786355782000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Macrophage metabolic reprogramming in organ transplantation: mechanisms, transplant outcomes, and therapeutic implications"],"prefix":"10.3389","volume":"16","author":[{"given":"Shaofeng","family":"Chen","sequence":"first","affiliation":[{"name":"Nankai University School of Medicine","place":["Tianjin, China"]},{"name":"Tianjin First Central Hospital, Organ Transplantation Research Center","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejun","family":"Kong","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Laboratory for Clinical Medicine, Capital Medical University","place":["Beijing, China"]},{"name":"Capital Medical University, State Key Laboratory of Digestive Health","place":["Beijing, China"]},{"name":"Beijing Key Laboratory of Organ Cultivation and Organ Protection in Transplantation, Beijing Friendship Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"Clinical Center for Pediatric Liver Transplantation, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeqi","family":"Nian","sequence":"additional","affiliation":[{"name":"Department of Renal Transplantation, Tianjin First Central Hospital, Nankai University","place":["Tianjin, China"]},{"name":"Institute of Transplantation Medicine, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenglu","family":"Wang","sequence":"additional","affiliation":[{"name":"Biological Sample Resource Sharing Center, Tianjin First Central Hospital","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Tianjin First Central Hospital, Organ Transplantation Research Center","place":["Tianjin, China"]},{"name":"Institute of Transplantation Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital","place":["Tianjin, China"]},{"name":"Key Laboratory of Transplant Medicine, Chinese Academy of Medical Science","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111370","article-title":"Advances in macrophage metabolic reprogramming in myocardial ischemia-reperfusion","volume":"123","author":"Ao-Di","year":"2024","journal-title":"Cell. Signal."},{"key":"B2","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.cmet.2016.10.008","article-title":"Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity","volume":"24","author":"Arts","year":"2016","journal-title":"Cell Metab."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3816","DOI":"10.1038\/s41467-020-17669-5","article-title":"Stat3 serine phosphorylation is required for tlr4 metabolic reprogramming and il-1\u03b2 expression","volume":"11","author":"Balic","year":"2020","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"999","DOI":"10.4049\/jimmunol.1601318","article-title":"Targeting metabolism as a novel therapeutic approach to autoimmunity, inflammation, and transplantation","volume":"198","author":"Bettencourt","year":"2017","journal-title":"J. Immunol. (Baltimore Md. 1950)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.ajt.2025.10.013","article-title":"Erythropoietin prolongs graft survival in mice by counteracting trained immunity","volume":"26","author":"Bin","year":"2026","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B6","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.kint.2017.01.029","article-title":"Macrophage density in early surveillance biopsies predicts future renal transplant function","volume":"92","author":"Br\u00e4sen","year":"2017","journal-title":"Kidney Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.immuni.2018.09.008","article-title":"Inhibiting inflammation with myeloid cell-specific nanobiologics promotes organ transplant acceptance","volume":"49","author":"Braza","year":"2018","journal-title":"Immunity"},{"key":"B8","first-page":"2010","article-title":"Atg16l1 promotes lung transplant tolerance by regulating glycolysis in macrophages","volume-title":"Biorxiv : The Preprint Server for Biology","author":"Cano","year":"2025"},{"key":"B9","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s00395-021-00904-5","article-title":"Single-cell transcriptomic identified hif1a as a target for attenuating acute rejection after heart transplantation","volume":"116","author":"Chang","year":"2021","journal-title":"Basic. Res. Cardiol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115678","article-title":"Msc-derived exosomes carrying sfgl2 alleviate acute rejection of mouse heart transplantation by regulating macrophage polarization","volume":"167","author":"Chen","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1097\/TP.0000000000004899","article-title":"Mek1\/2-pkm2 pathway modulates the immunometabolic reprogramming of proinflammatory allograft-infiltrating macrophages during heart transplant rejection","volume":"108","author":"Chen","year":"2024","journal-title":"Transplantation"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114711","article-title":"Notch signaling orchestrates the inflammatory-fibrotic continuum of macrophages in renal allograft rejection","volume":"452","author":"Chen","year":"2025","journal-title":"Exp. Cell. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/nature13909","article-title":"Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ros","volume":"515","author":"Chouchani","year":"2014","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12943-024-02064-1","article-title":"Decoding the spatiotemporal heterogeneity of tumor-associated macrophages","volume":"23","author":"Chu","year":"2024","journal-title":"Mol. Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2319623121","article-title":"Hypoxia inducible factor 2\u03b1 promotes tolerogenic macrophage development during cardiac transplantation through transcriptional regulation of colony stimulating factor 1 receptor","volume":"121","author":"DeBerge","year":"2024","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B16","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.molcel.2010.06.022","article-title":"Activation of a metabolic gene regulatory network downstream of mtor complex 1","volume":"39","author":"D\u00fcvel","year":"2010","journal-title":"Mol. Cell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.smim.2015.09.001","article-title":"Contribution of metabolic reprogramming to macrophage plasticity and function","volume":"27","author":"El Kasmi","year":"2015","journal-title":"Semin. Immunol."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202200128R","article-title":"Macrophage programming is regulated by a cooperative interaction between fatty acid binding protein 5 and peroxisome proliferator-activated receptor \u03b3","volume":"36","author":"El Kharbili","year":"2022","journal-title":"FASEB J. Off. Publ. Fed. Am. Societies For. Exp. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"4034","DOI":"10.1038\/s41598-019-40619-1","article-title":"The nlrp3 inflammasome modulates glycolysis by increasing pfkfb3 in an il-1\u03b2-dependent manner in macrophages","volume":"9","author":"Finucane","year":"2019","journal-title":"Sci. Rep."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00420","article-title":"Metabolic reprograming in macrophage polarization","volume":"5","author":"Galv\u00e1n-Pe\u00f1a","year":"2014","journal-title":"Front. Immunol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/cells11030404","article-title":"Multistability in macrophage activation pathways and metabolic implications","volume":"11","author":"Gei\u00df","year":"2022","journal-title":"Cells"},{"key":"B22","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41589-020-0533-x","article-title":"A small molecule g6pd inhibitor reveals immune dependence on pentose phosphate pathway","volume":"16","author":"Ghergurovich","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1007\/s40620-020-00726-z","article-title":"Kidney allograft fibrosis: what we learned from latest translational research studies","volume":"33","author":"Granata","year":"2020","journal-title":"J. Nephrol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"628","DOI":"10.17179\/excli2020-3053","article-title":"Metabolic reprogramming of macrophages and its involvement in inflammatory diseases","volume":"20","author":"Guo","year":"2021","journal-title":"Excil J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1097\/01.mnh.0000444811.26884.2d","article-title":"Chronic allograft nephropathy or interstitial fibrosis and tubular atrophy: what is in a name","volume":"23","author":"Haas","year":"2014","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"B26","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/978-3-031-65944-7_12","article-title":"Unlocking macrophage secrets: histone deacetylases in chronic transplant rejection","volume":"74","author":"Halasa","year":"2024","journal-title":"Results Problems Cell. Differentiation"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2624","DOI":"10.2337\/db16-0060","article-title":"Glucose-6-phosphate dehydrogenase deficiency improves insulin resistance with reduced adipose tissue inflammation in obesity","volume":"65","author":"Ham","year":"2016","journal-title":"Diabetes"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2026.1721230","article-title":"Mitochondrial metabolic reprogramming, quality control, and intercellular transfer in regulating macrophage plasticity","volume":"17","author":"He","year":"2026","journal-title":"Front. Physiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1172\/JCI30487","article-title":"Hypoxia promotes fibrogenesis in vivo via hif-1 stimulation of epithelial-to-mesenchymal transition","volume":"117","author":"Higgins","year":"2007","journal-title":"J. Clin. Invest."},{"key":"B30","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.cellsig.2017.02.019","article-title":"Role of akt\/pkb and pfkfb isoenzymes in the control of glycolysis, cell proliferation and protein synthesis in mitogen-stimulated thymocytes","volume":"34","author":"Houddane","year":"2017","journal-title":"Cell. Signal."},{"key":"B31","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","article-title":"Metabolic reprogramming mediated by the mtorc2-irf4 signaling axis is essential for macrophage alternative activation","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"},{"key":"B32","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bbrc.2013.09.037","article-title":"Atp-citrate lyase is essential for macrophage inflammatory response","volume":"440","author":"Infantino","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.immuni.2015.02.005","article-title":"Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization","volume":"42","author":"Jha","year":"2015","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/s43018-025-00909-2","article-title":"Linking macrophage metabolism to function in the tumor microenvironment","volume":"6","author":"Jin","year":"2025","journal-title":"Nat. Cancer"},{"key":"B35","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nature12154","article-title":"A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence","volume":"498","author":"Kaplon","year":"2013","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3277","DOI":"10.1172\/JCI124012","article-title":"Enhanced glycolytic metabolism supports transmigration of brain-infiltrating macrophages in multiple sclerosis","volume":"129","author":"Kaushik","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B37","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1159\/000516780","article-title":"Metabolic regulation of macrophage activation","volume":"14","author":"Kolliniati","year":"2022","journal-title":"J. Innate Immun."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202451321","article-title":"Metabolic reprogramming of fibroblastic reticular cells in immunity and tolerance","volume":"55","author":"Kong","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1161\/CIRCULATIONAHA.121.057400","article-title":"Donor macrophages modulate rejection after heart transplantation","volume":"146","author":"Kopecky","year":"2022","journal-title":"Circulation"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1097\/IN9.0000000000000038","article-title":"Inflammaging and fatty acid oxidation in monocytes and macrophages","volume":"6","author":"Kruglov","year":"2024","journal-title":"Immunometabolism (Cobham Surrey)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098257","article-title":"Multiple shades of gray-macrophages in acute allograft rejection","volume":"24","author":"Lackner","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"7503","DOI":"10.4049\/jimmunol.178.12.7503","article-title":"The innate immune system in allograft rejection and tolerance","volume":"178","author":"LaRosa","year":"2007","journal-title":"J. Immunol. (Baltimore Md. 1950)"},{"key":"B43","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.immuni.2019.11.009","article-title":"Toll-like receptor signaling rewires macrophage metabolism and promotes histone acetylation via atp-citrate lyase","volume":"51","author":"Lauterbach","year":"2019","journal-title":"Immunity"},{"key":"B44","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1007\/s00011-025-02109-1","article-title":"Pgc1\u03b1 alleviates m1 macrophage polarization through dual regulation of succinate metabolism and traf5 expression to mitigate tlr4\/nf-\u03bab-driven inflammatory cascades and myocardial ischemia\/reperfusion injury","volume":"74","author":"Leng","year":"2025","journal-title":"Inflammation Res. Off. J. Eur. Histamine Res. Soc. . [et al.]"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.115465","article-title":"Hexokinase 2-mediated metabolic stress and inflammation burden of liver macrophages via histone lactylation in masld","volume":"44","author":"Li","year":"2025","journal-title":"Cell Rep."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-024-01196-7","article-title":"Nf-\u03bab rela is a cell-intrinsic metabolic checkpoint restricting glycolysis","volume":"14","author":"Li","year":"2024","journal-title":"Cell. Bioscience"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e386","DOI":"10.1097\/TP.0000000000005386","article-title":"Tdo2 deficiency exacerbates the immune rejection response in rat liver transplantation via the kyn-ahr axis","volume":"109","author":"Li","year":"2025","journal-title":"Transplantation"},{"key":"B48","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/s41420-025-02461-5","article-title":"Nrf1 coordinates mitochondrial adaptations to dampen intracellular ros and inflammatory responses during ischemia reperfusion","volume":"11","author":"Li","year":"2025","journal-title":"Cell. Death Discov."},{"key":"B49","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s40472-016-0130-9","article-title":"Macrophages as effectors of acute and chronic allograft injury","volume":"3","author":"Liu","year":"2016","journal-title":"Curr. Transplant. Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e631","DOI":"10.1097\/TP.0000000000005461","article-title":"Pkm2 drives lactate-mediated fibrosis in liver transplantation","volume":"109","author":"Liu","year":"2025","journal-title":"Transplantation"},{"key":"B51","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1038\/ni.3796","article-title":"\u03b1-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming","volume":"18","author":"Liu","year":"2017","journal-title":"Nat. Immunol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002548","article-title":"S100a4 enhances protumor macrophage polarization by control of ppar-\u03b3-dependent induction of fatty acid oxidation","volume":"9","author":"Liu","year":"2021","journal-title":"J. ImmunoTher. Cancer"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2424534122","article-title":"Setdb1 ablation in macrophages attenuates fibrosis in heart allografts","volume":"122","author":"Ma","year":"2025","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.936167","article-title":"Role of metabolic reprogramming in pro-inflammatory cytokine secretion from lps or silica-activated macrophages","volume":"13","author":"Marrocco","year":"2022","journal-title":"Front. Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/s42255-019-0115-y","article-title":"Succinate accumulation drives ischaemia-reperfusion injury during organ transplantation","volume":"1","author":"Martin","year":"2019","journal-title":"Nat. Metab."},{"key":"B56","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41467-019-13668-3","article-title":"Mitochondrial tca cycle metabolites control physiology and disease","volume":"11","author":"Mart\u00ednez-Reyes","year":"2020","journal-title":"Nat. Commun."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1172\/JCI182480","article-title":"Acetyl-coa carboxylase 1 inhibition increases treg metabolism and graft-versus-host disease treatment efficacy via mitochondrial fusion","volume":"135","author":"McDonald-Hyman","year":"2025","journal-title":"J. Clin. Invest."},{"key":"B58","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/s12035-025-05549-2","article-title":"Calcineurin inhibitors: current role, toxicity management, and future frontiers in immunosuppression","volume":"63","author":"Mistry","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1600-065X.2011.01009.x","article-title":"Innate immunity in transplant tolerance and rejection","volume":"241","author":"Murphy","year":"2011","journal-title":"Immunol. Rev."},{"key":"B60","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s40264-019-00810-9","article-title":"Sirolimus and mtor inhibitors: a review of side effects and specific management in solid organ transplantation","volume":"42","author":"Nguyen","year":"2019","journal-title":"Drug Saf."},{"key":"B61","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1615\/CritRevImmunol.2025057969","article-title":"Understanding the impact of calcineurin inhibitors on t cell regulation: mechanisms and clinical implications","volume":"45","author":"Nimbarte","year":"2025","journal-title":"Crit. Rev. Immunol."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi8602","article-title":"Lactate supports a metabolic-epigenetic link in macrophage polarization","volume":"7","author":"Noe","year":"2021","journal-title":"Sci. Adv."},{"key":"B63","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/ni.3366","article-title":"Fatty acid oxidation in macrophage polarization","volume":"17","author":"Nomura","year":"2016","journal-title":"Nat. Immunol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/ajt.15620","article-title":"Trained immunity in organ transplantation","volume":"20","author":"Ochando","year":"2020","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B65","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41581-022-00633-5","article-title":"Trained immunity - basic concepts and contributions to immunopathology","volume":"19","author":"Ochando","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.kint.2023.06.022","article-title":"Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion","volume":"104","author":"Oh","year":"2023","journal-title":"Kidney Int."},{"key":"B67","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1097\/TP.0000000000004978","article-title":"Targeting macrophages in organ transplantation: a step toward personalized medicine","volume":"108","author":"Owen","year":"2024","journal-title":"Transplantation"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3720","DOI":"10.1016\/j.cell.2022.08.018","article-title":"Mtor-regulated mitochondrial metabolism limits mycobacterium-induced cytotoxicity","volume":"185","author":"Pag\u00e1n","year":"2022","journal-title":"Cell."},{"key":"B69","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.cmet.2015.01.017","article-title":"Pyruvate kinase m2 regulates hif-1\u03b1 activity and il-1\u03b2 induction and is a critical determinant of the warburg effect in lps-activated macrophages","volume":"21","author":"Palsson-McDermott","year":"2015","journal-title":"Cell Metab."},{"key":"B70","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1080\/21623945.2017.1288321","article-title":"The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in obesity","volume":"6","author":"Park","year":"2017","journal-title":"Adipocyte"},{"key":"B71","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.bbalip.2009.09.017","article-title":"Lipotoxicity in macrophages: evidence from diseases associated with the metabolic syndrome","volume":"1801","author":"Prieur","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.2967\/jnumed.110.078550","article-title":"Potential of noninvasive serial assessment of acute renal allograft rejection by 18f-fdg pet to monitor treatment efficiency","volume":"51","author":"Reuter","year":"2010","journal-title":"J. Nucl. Med. Off. Publication Soc. Nucl. Med."},{"key":"B73","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/nature06905","article-title":"Nf-kappab links innate immunity to the hypoxic response through transcriptional regulation of hif-1alpha","volume":"453","author":"Rius","year":"2008","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.semcancer.2008.11.010","article-title":"Is akt the \"warburg kinase\"?-Akt-energy metabolism interactions and oncogenesis","volume":"19","author":"Robey","year":"2009","journal-title":"Semin. Cancer Biol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1007\/s00018-007-6380-z","article-title":"Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in treating diabetes, heart ischemia, and cancer","volume":"64","author":"Roche","year":"2007","journal-title":"Cell. Mol. Life. Sci. CMLS"},{"key":"B76","doi-asserted-by":"publisher","first-page":"18217","DOI":"10.1074\/jbc.M110.101048","article-title":"Extended ischemia prevents hif1alpha degradation at reoxygenation by impairing prolyl-hydroxylation: role of krebs cycle metabolites","volume":"285","author":"Serra-P\u00e9rez","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B77","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.ajt.2025.08.026","article-title":"Suppression of cardiac allograft vasculopathy by a macrophage efferocytosis receptor","volume":"26","author":"Shah","year":"2026","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B78","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1038\/s41401-023-01222-3","article-title":"Macrophages promote the transition from myocardial ischemia reperfusion injury to cardiac fibrosis in mice through gmcsf\/ccl2\/ccr2 and phenotype switching","volume":"45","author":"Shen","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.ajt.2026.01.015","article-title":"Tubule-derived growth differentiation factor 15 limits renal transplant injury by reprogramming macrophage responses","volume":"26","author":"Shi","year":"2026","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B80","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1084\/jem.20150900","article-title":"The glycolytic enzyme pkm2 bridges metabolic and inflammatory dysfunction in coronary artery disease","volume":"213","author":"Shirai","year":"2016","journal-title":"J. Exp. Med."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306062","article-title":"Inorganic phosphate as \"bioenergetic messenger\" triggers m2-type macrophage polarization","volume":"11","author":"Sun","year":"2024","journal-title":"Advanced Sci. (Weinheim Baden-Wurttemberg Germany)"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108395","article-title":"Dimethyl fumarate attenuates lps induced septic acute kidney injury by suppression of nf\u03bab p65 phosphorylation and macrophage activation","volume":"102","author":"Tang","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B83","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces il-1\u03b2 through hif-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"B84","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1111\/ajt.12803","article-title":"The role of macrophages in the development of human renal allograft fibrosis in the first year after transplantation","volume":"14","author":"Toki","year":"2014","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3390\/biology15020162","article-title":"Macrophages in chronic rejection: the shapeshifters behind transplant survival","volume":"15","author":"Uosef","year":"2026","journal-title":"Biology"},{"key":"B86","doi-asserted-by":"publisher","first-page":"3280","DOI":"10.1111\/ajt.16581","article-title":"Mir-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy","volume":"21","author":"Usuelli","year":"2021","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512032","article-title":"Impact of lipid metabolism on macrophage polarization: implications for inflammation and tumor immunity","volume":"24","author":"Vassiliou","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01462","article-title":"The metabolic signature of macrophage responses","volume":"10","author":"Viola","year":"2019","journal-title":"Front. Immunol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1681\/ASN.2016050573","article-title":"Macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury","volume":"28","author":"Wang","year":"2017","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9029327","article-title":"Hif1\u03b1-induced glycolysis metabolism is essential to the activation of inflammatory macrophages","volume":"2017","author":"Wang","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1776694","article-title":"Immunometabolic remodeling: new perspectives and strategies for liver transplantation","volume":"17","author":"Wang","year":"2026","journal-title":"Front. Immunol."},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1670370","article-title":"Visualizing early allograft rejection: an m1 macrophage-specific glut1 probe predicts tcmr onset in renal transplantation","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Immunol."},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00141","article-title":"A role for the krebs cycle intermediate citrate in metabolic reprogramming in innate immunity and inflammation","volume":"9","author":"Williams","year":"2018","journal-title":"Front. Immunol."},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.177334","article-title":"Myeloid drp1 deficiency limits revascularization in ischemic muscles via inflammatory macrophage polarization and metabolic reprogramming","volume":"10","author":"Yadav","year":"2025","journal-title":"JCI Insight"},{"key":"B95","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1177\/15353702221080130","article-title":"Macrophage polarization in hypoxia and ischemia\/reperfusion: insights into the role of energetic metabolism","volume":"247","author":"Yakupova","year":"2022","journal-title":"Exp. Biol. Med. (Maywood N.J.)"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202412123","article-title":"Mettl3 potentiates m2 macrophage-driven mmt to aggravate renal allograft fibrosis via the tgf-\u03b21\/smad3 pathway","volume":"12","author":"Yao","year":"2025","journal-title":"Advanced Sci. (Weinheim Baden-Wurttemberg Germany)"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.141593","article-title":"Lilrb3 (ilt5) is a myeloid cell checkpoint that elicits profound immunomodulation","volume":"5","author":"Yeboah","year":"2020","journal-title":"JCI Insight"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1002\/JPER.21-0227","article-title":"Hexokinase 2-mediated glycolysis promotes receptor activator of nf-\u03bab ligand expression in porphyromonas gingivalis lipopolysaccharide-treated osteoblasts","volume":"93","author":"Yu","year":"2022","journal-title":"J. Periodontol."},{"key":"B99","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.cmet.2018.12.004","article-title":"Efferocytosis fuels requirements of fatty acid oxidation and the electron transport chain to polarize macrophages for tissue repair","volume":"29","author":"Zhang","year":"2019","journal-title":"Cell Metab."},{"key":"B100","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.ajt.2024.11.021","article-title":"Graft-derived extracellular vesicles transport mirnas to modulate macrophage polarization after heart transplantation","volume":"25","author":"Zheng","year":"2025","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transplant. Surgeons"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.151596","article-title":"Targeting fatty acid \u03b2-oxidation impairs monocyte differentiation and prolongs heart allograft survival","volume":"7","author":"Zhu","year":"2022","journal-title":"JCI Insight"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1868319\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:56:24Z","timestamp":1786355784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1868319\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":101,"alternative-id":["10.3389\/fcimb.2026.1868319"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1868319","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]},"article-number":"1868319"}}