Skip to main content

Immunometabolism and Organ Transplantation

  • Chapter
  • First Online:
Essential Aspects of Immunometabolism in Health and Disease

Abstract

Inflammation fundamentally influences short and long-term performance of solid organ allografts. Thus, it is relevant to control inflammatory processes to maintain graft function and survival.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gueler F, Gwinner W, Schwarz A, Haller H (2004) Long-term effects of acute ischemia and reperfusion injury. Kidney Int 66(2):523–527. https://doi.org/10.1111/j.1523-1755.2004.761_11.x

    Article  PubMed  Google Scholar 

  2. Furuichi K, Wada T, Kaneko S, Murphy PM (2008) Roles of chemokines in renal ischemia/reperfusion injury. Front Biosci 13:4021–4028. https://doi.org/10.2741/2990

    Article  CAS  PubMed  Google Scholar 

  3. Eming SA, Wynn TA, Martin P (2017) Inflammation and metabolism in tissue repair and regeneration. Science 356(6342):1026–1030. https://doi.org/10.1126/science.aam7928

    Article  CAS  PubMed  Google Scholar 

  4. Gaber T, Strehl C, Buttgereit F (2017) Metabolic regulation of inflammation. Nat Rev Rheumatol 13(5):267–279. https://doi.org/10.1038/nrrheum.2017.37

    Article  PubMed  Google Scholar 

  5. Allocco JB, Alegre ML (2020) Exploiting immunometabolism and T cell function for solid organ transplantation. Cell Immunol 351. https://doi.org/10.1016/j.cellimm.2020.104068

  6. Domínguez-Amorocho O, Takiishi T, da Cunha FF, Camara NOS (2019) Immunometabolism: a target for the comprehension of immune response toward transplantation. World J Transplant 9(2):27–34. https://doi.org/10.5500/wjt.v9.i2.27

    Article  PubMed  PubMed Central  Google Scholar 

  7. Tanimine N, Turka LA, Priyadharshini B (2018) Navigating T-cell immunometabolism in transplantation. Transplantation 102(2):230–239. https://doi.org/10.1097/tp.0000000000001951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mathis D, Shoelson SE (2011) Immunometabolism: an emerging frontier. Nat Rev Immunol 11(2):81. https://doi.org/10.1038/nri2922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Makowski L, Chaib M, Rathmell JC (2020) Immunometabolism: from basic mechanisms to translation. Immunol Rev 295(1):5–14. https://doi.org/10.1111/imr.12858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Buck MD, Sowell RT, Kaech SM, Pearce EL (2017) Metabolic instruction of immunity. Cell 169(4):570–586. https://doi.org/10.1016/j.cell.2017.04.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hosomi K, Kunisawa J (2020) Diversity of energy metabolism in immune responses regulated by micro-organisms and dietary nutrition. Int Immunol 32(7):447–454. https://doi.org/10.1093/intimm/dxaa020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kelly PN (2019) Metabolism as a driver of immune response. Science 363(6423):137–139. https://doi.org/10.1126/science.363.6423.137-j

    Article  Google Scholar 

  13. Palmer CS, Ostrowski M, Balderson B, Christian N, Crowe SM (2015) Glucose metabolism regulates T cell activation, differentiation, and functions. Front Immunol 6:1. https://doi.org/10.3389/fimmu.2015.00001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Pearce EL, Pearce EJ (2013) Metabolic pathways in immune cell activation and quiescence. Immunity 38(4):633–643. https://doi.org/10.1016/j.immuni.2013.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. O’Neill LA, Kishton RJ, Rathmell J (2016) A guide to immunometabolism for immunologists. Nat Rev Immunol 16(9):553–565. https://doi.org/10.1038/nri.2016.70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stincone A, Prigione A, Cramer T, Wamelink MM, Campbell K, Cheung E, Olin-Sandoval V, Grüning NM, Krüger A, Tauqeer Alam M, Keller MA, Breitenbach M, Brindle KM, Rabinowitz JD, Ralser M (2015) The return of metabolism: biochemistry and physiology of the pentose phosphate pathway. Biol Rev Camb Philos Soc 90(3):927–963. https://doi.org/10.1111/brv.12140

    Article  PubMed  Google Scholar 

  17. Ochando J, Fayad ZA, Madsen JC, Netea MG, Mulder WJM (2020) Trained immunity in organ transplantation. Am J Transplant 20(1):10–18. https://doi.org/10.1111/ajt.15620

    Article  PubMed  Google Scholar 

  18. Johnson AR, Milner JJ, Makowski L (2012) The inflammation highway: metabolism accelerates inflammatory traffic in obesity. Immunol Rev 249(1):218–238. https://doi.org/10.1111/j.1600-065X.2012.01151.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dasu MR, Jialal I (2011) Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors. Am J Physiol Endocrinol Metab 300(1):E145-154. https://doi.org/10.1152/ajpendo.00490.2010

    Article  CAS  PubMed  Google Scholar 

  20. Martinez-Llordella M, Mastoridis S (2018) Immunometabolism: novel monitoring and therapeutic approach in transplantation. Transplantation 102(2):187–188. https://doi.org/10.1097/tp.0000000000001988

    Article  PubMed  Google Scholar 

  21. Sim WJ, Ahl PJ, Connolly JE (2016) Metabolism is central to tolerogenic dendritic cell function. Mediators Inflamm 2016:2636701. https://doi.org/10.1155/2016/2636701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wrenshall L (2003) Role of the microenvironment in immune responses to transplantation. Springer Semin Immunopathol 25(2):199–213. https://doi.org/10.1007/s00281-003-0138-y

    Article  CAS  PubMed  Google Scholar 

  23. Qu Q, Zeng F, Liu X, Wang QJ, Deng F (2016) Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer. Cell Death Dis 7(5). https://doi.org/10.1038/cddis.2016.132

  24. Macintyre AN, Gerriets VA, Nichols AG, Michalek RD, Rudolph MC, Deoliveira D, Anderson SM, Abel ED, Chen BJ, Hale LP, Rathmell JC (2014) The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function. Cell Metab 20(1):61–72. https://doi.org/10.1016/j.cmet.2014.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nakaya M, Xiao Y, Zhou X, Chang JH, Chang M, Cheng X, Blonska M, Lin X, Sun SC (2014) Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity 40(5):692–705. https://doi.org/10.1016/j.immuni.2014.04.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lee CF, Lo YC, Cheng CH, Furtmüller GJ, Oh B, Andrade-Oliveira V, Thomas AG, Bowman CE, Slusher BS, Wolfgang MJ, Brandacher G, Powell JD (2015) Preventing allograft rejection by targeting immune metabolism. Cell Rep 13(4):760–770. https://doi.org/10.1016/j.celrep.2015.09.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Nguyen HD, Chatterjee S, Haarberg KM, Wu Y, Bastian D, Heinrichs J, Fu J, Daenthanasanmak A, Schutt S, Shrestha S, Liu C, Wang H, Chi H, Mehrotra S, Yu XZ (2016) Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation. J Clin Invest 126(4):1337–1352. https://doi.org/10.1172/jci82587

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ochando J, Ordikhani F, Boros P, Jordan S (2019) The innate immune response to allotransplants: mechanisms and therapeutic potentials. Cell Mol Immunol 16(4):350–356. https://doi.org/10.1038/s41423-019-0216-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Salvadori M, Rosso G, Bertoni E (2015) Update on ischemia-reperfusion injury in kidney transplantation: pathogenesis and treatment. World J Transplant 5(2):52–67. https://doi.org/10.5500/wjt.v5.i2.52

    Article  PubMed  PubMed Central  Google Scholar 

  30. Tian R, Abel ED (2001) Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis. Circulation 103(24):2961–2966. https://doi.org/10.1161/01.cir.103.24.2961

    Article  CAS  PubMed  Google Scholar 

  31. Marelli-Berg FM, Aksentijevic D (2019) Immunometabolic cross-talk in the inflamed heart. Cell Stress 3(8):240–266. https://doi.org/10.15698/cst2019.08.194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Miller EJ, Li J, Leng L, McDonald C, Atsumi T, Bucala R, Young LH (2008) Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature 451(7178):578–582. https://doi.org/10.1038/nature06504

    Article  CAS  PubMed  Google Scholar 

  33. Davis CK, Jain SA, Bae ON, Majid A, Rajanikant GK (2018) Hypoxia mimetic agents for ischemic stroke. Front Cell Dev Biol 6:175. https://doi.org/10.3389/fcell.2018.00175

    Article  PubMed  Google Scholar 

  34. Zhang Z, Yao L, Yang J, Wang Z, Du G (2018) PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review). Mol Med Rep 18(4):3547–3554. https://doi.org/10.3892/mmr.2018.9375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord ENJ, Smith AC, Eyassu F, Shirley R, Hu CH, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa ASH, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515(7527):431–435. https://doi.org/10.1038/nature13909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Inserte J, Garcia-Dorado D, Hernando V, Barba I, Soler-Soler J (2006) Ischemic preconditioning prevents calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion. Cardiovasc Res 70(2):364–373. https://doi.org/10.1016/j.cardiores.2006.02.017

    Article  CAS  PubMed  Google Scholar 

  37. Kahn J, Schemmer P (2018) Control of ischemia-reperfusion injury in liver transplantation: potentials for increasing the donor pool. Visc Med 34(6):444–448. https://doi.org/10.1159/000493889

    Article  PubMed  PubMed Central  Google Scholar 

  38. Martins RM, Teodoro JS, Furtado E, Rolo AP, Palmeira CM, Tralhão JG (2018) Recent insights into mitochondrial targeting strategies in liver transplantation. Int J Med Sci 15(3):248–256. https://doi.org/10.7150/ijms.22891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kozlov AV, Lancaster JR Jr, Meszaros AT, Weidinger A (2017) Mitochondria-meditated pathways of organ failure upon inflammation. Redox Biol 13:170–181. https://doi.org/10.1016/j.redox.2017.05.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhou H, Zhu P, Wang J, Zhu H, Ren J, Chen Y (2018) Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2α-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ 25(6):1080–1093. https://doi.org/10.1038/s41418-018-0086-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lakkis FG, Li XC (2018) Innate allorecognition by monocytic cells and its role in graft rejection. Am J Transplant 18(2):289–292. https://doi.org/10.1111/ajt.14436

    Article  CAS  PubMed  Google Scholar 

  42. Lin CM, Gill RG (2016) Direct and indirect allograft recognition: pathways dictating graft rejection mechanisms. Curr Opin Organ Transplant 21(1):40–44. https://doi.org/10.1097/mot.0000000000000263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Priyadharshini B, Turka LA (2015) T-cell energy metabolism as a controller of cell fate in transplantation. Curr Opin Organ Transplant 20(1):21–28. https://doi.org/10.1097/mot.0000000000000149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. da Silva MB, da Cunha FF, Terra FF, Camara NO (2017) Old game, new players: linking classical theories to new trends in transplant immunology. World J Transplant 7(1):1–25. https://doi.org/10.5500/wjt.v7.i1.1

    Article  PubMed  PubMed Central  Google Scholar 

  45. Thwe PM, Pelgrom LR, Cooper R, Beauchamp S, Reisz JA, D’Alessandro A, Everts B, Amiel E (2019) Cell-Intrinsic glycogen metabolism supports early glycolytic reprogramming required for dendritic cell immune responses. Cell Metab 30(1):225. https://doi.org/10.1016/j.cmet.2019.05.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Svajger U, Obermajer N, Jeras M (2010) Dendritic cells treated with resveratrol during differentiation from monocytes gain substantial tolerogenic properties upon activation. Immunology 129(4):525–535. https://doi.org/10.1111/j.1365-2567.2009.03205.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Liu Z, Fan H, Jiang S (2013) CD4(+) T-cell subsets in transplantation. Immunol Rev 252(1):183–191. https://doi.org/10.1111/imr.12038

    Article  CAS  PubMed  Google Scholar 

  48. Chai H, Yang L, Gao L, Guo Y, Li H, Fan X, Wu B, Xue S, Cai Y, Jiang X, Qin B, Zhang S, Ke Y (2014) Decreased percentages of regulatory T cells are necessary to activate Th1-Th17-Th22 responses during acute rejection of the peripheral nerve xenotransplantation in mice. Transplantation 98(7):729–737. https://doi.org/10.1097/tp.0000000000000319

    Article  CAS  PubMed  Google Scholar 

  49. Hall BM (2016) CD4+CD25+ T regulatory cells in transplantation tolerance: 25 years on. Transplantation 100(12):2533–2547. https://doi.org/10.1097/tp.0000000000001436

    Article  CAS  PubMed  Google Scholar 

  50. Xu X, Huang H, Wang Q, Cai M, Qian Y, Han Y, Wang X, Gao Y, Yuan M, Xu L, Yao C, Xiao L, Shi B (2017) IFN-γ-producing Th1-like regulatory T cells may limit acute cellular renal allograft rejection: Paradoxical post-transplantation effects of IFN-γ. Immunobiology 222(2):280–290. https://doi.org/10.1016/j.imbio.2016.09.012

    Article  CAS  PubMed  Google Scholar 

  51. Gerriets VA, Kishton RJ, Nichols AG, Macintyre AN, Inoue M, Ilkayeva O, Winter PS, Liu X, Priyadharshini B, Slawinska ME, Haeberli L, Huck C, Turka LA, Wood KC, Hale LP, Smith PA, Schneider MA, MacIver NJ, Locasale JW, Newgard CB, Shinohara ML, Rathmell JC (2015) Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. J Clin Invest 125(1):194–207. https://doi.org/10.1172/jci76012

    Article  PubMed  Google Scholar 

  52. Shan J, Jin H, Xu Y (2020) T cell metabolism: a new perspective on Th17/treg cell imbalance in systemic lupus erythematosus. Front Immunol 11(1027). https://doi.org/10.3389/fimmu.2020.01027

  53. Xu T, Stewart KM, Wang X, Liu K, Xie M, Ryu JK, Li K, Ma T, Wang H, Ni L, Zhu S, Cao N, Zhu D, Zhang Y, Akassoglou K, Dong C, Driggers EM, Ding S (2017) Metabolic control of T(H)17 and induced T(reg) cell balance by an epigenetic mechanism. Nature 548(7666):228–233. https://doi.org/10.1038/nature23475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168(6):960–976. https://doi.org/10.1016/j.cell.2017.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Siu JHY, Surendrakumar V, Richards JA, Pettigrew GJ (2018) T cell allorecognition pathways in solid organ transplantation. Front Immunol 9:2548. https://doi.org/10.3389/fimmu.2018.02548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Azzi JR, Sayegh MH, Mallat SG (2013) Calcineurin inhibitors: 40 years later, can’t live without. J Immunol 191(12):5785–5791. https://doi.org/10.4049/jimmunol.1390055

    Article  CAS  PubMed  Google Scholar 

  57. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, Bordman Z, Fu J, Kim Y, Yen HR, Luo W, Zeller K, Shimoda L, Topalian SL, Semenza GL, Dang CV, Pardoll DM, Pan F (2011) Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146(5):772–784. https://doi.org/10.1016/j.cell.2011.07.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kurebayashi Y, Nagai S, Ikejiri A, Ohtani M, Ichiyama K, Baba Y, Yamada T, Egami S, Hoshii T, Hirao A, Matsuda S, Koyasu S (2012) PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORgamma. Cell Rep 1(4):360–373. https://doi.org/10.1016/j.celrep.2012.02.007

    Article  CAS  PubMed  Google Scholar 

  59. Shi LZ, Wang R, Huang G, Vogel P, Neale G, Green DR, Chi H (2011) HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J Exp Med 208(7):1367–1376. https://doi.org/10.1084/jem.20110278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rockey DC, Bell PD, Hill JA (2015) Fibrosis–a common pathway to organ injury and failure. N Engl J Med 372(12):1138–1149. https://doi.org/10.1056/NEJMra1300575

    Article  CAS  PubMed  Google Scholar 

  61. Li T, Zhang Z, Bartolacci JG, Dwyer GK, Liu Q, Mathews L, Velayutham M, Roessing A, Lee YC, Dai H, Shiva S, Oberbarnscheidt MH, Dziki JL, Mullett SJ, Wendell SG, Wilkinson JD, Webber SA, Wood-Trageser MA, Watkins SC, Demetris AJ, Hussey GS, Badylak SF, Turnquist HR (2020) Graft IL-33 regulates infiltrating macrophages to protect against chronic rejection. J Clin Invest. https://doi.org/10.1172/jci133008

    Article  PubMed  PubMed Central  Google Scholar 

  62. Mills EL, Kelly B, Logan A, Costa ASH, Varma M, Bryant CE, Tourlomousis P, Däbritz JHM, Gottlieb E, Latorre I, Corr SC, McManus G, Ryan D, Jacobs HT, Szibor M, Xavier RJ, Braun T, Frezza C, Murphy MP, O’Neill LA (2016) Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167(2):457-470.e413. https://doi.org/10.1016/j.cell.2016.08.064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Boucault L, Séverine B, Ossart J, Guillonneau C (2016) Tolerance in organ transplantation. frontiers-in-transplantology, Chap 3. https://doi.org/10.5772/62653

  64. Mondanelli G, Bianchi R, Pallotta MT, Orabona C, Albini E, Iacono A, Belladonna ML, Vacca C, Fallarino F, Macchiarulo A, Ugel S, Bronte V, Gevi F, Zolla L, Verhaar A, Peppelenbosch M, Mazza EMC, Bicciato S, Laouar Y, Santambrogio L, Puccetti P, Volpi C, Grohmann U (2017) A relay pathway between arginine and tryptophan metabolism confers immunosuppressive properties on dendritic cells. Immunity 46(2):233–244. https://doi.org/10.1016/j.immuni.2017.01.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127(6):1109–1122. https://doi.org/10.1016/j.cell.2006.11.013

    Article  CAS  PubMed  Google Scholar 

  66. Macdougall CE, Wood EG, Loschko J, Scagliotti V, Cassidy FC, Robinson ME, Feldhahn N, Castellano L, Voisin MB, Marelli-Berg F, Gaston-Massuet C, Charalambous M, Longhi MP (2018) Visceral adipose tissue immune homeostasis is regulated by the crosstalk between adipocytes and dendritic cell subsets. Cell Metab 27(3):588-601.e584. https://doi.org/10.1016/j.cmet.2018.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhao F, Xiao C, Evans KS, Theivanthiran T, DeVito N, Holtzhausen A, Liu J, Liu X, Boczkowski D, Nair S, Locasale JW, Hanks BA (2018) Paracrine Wnt5a-β-catenin signaling triggers a metabolic program that drives dendritic cell tolerization. Immunity 48(1):147-160.e147. https://doi.org/10.1016/j.immuni.2017.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Chen Y, Li D, Tsang JY, Niu N, Peng J, Zhu J, Hui K, Xu A, Lui VC, Lamb JR, Tam PK (2011) PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class II-mismatched cardiac grafts. J Heart Lung Transplant 30(6):698–706. https://doi.org/10.1016/j.healun.2011.01.704

    Article  PubMed  Google Scholar 

  69. Zhu HC, Qiu T, Liu XH, Dong WC, Weng XD, Hu CH, Kuang YL, Gao RH, Dan C, Tao T (2012) Tolerogenic dendritic cells generated by RelB silencing using shRNA prevent acute rejection. Cell Immunol 274(1–2):12–18. https://doi.org/10.1016/j.cellimm.2012.02.012

    Article  CAS  PubMed  Google Scholar 

  70. Adorini L, Penna G, Giarratana N, Uskokovic M (2003) Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem 88(2):227–233. https://doi.org/10.1002/jcb.10340

    Article  CAS  PubMed  Google Scholar 

  71. Liu GY, Sabatini DM (2020) mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol 21(4):183–203. https://doi.org/10.1038/s41580-019-0199-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Sabatini DM (2017) Twenty-five years of mTOR: uncovering the link from nutrients to growth. Proc Natl Acad Sci U S A 114(45):11818–11825. https://doi.org/10.1073/pnas.1716173114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Chung BH, Oh HJ, Piao SG, Sun IO, Kang SH, Choi SR, Park HS, Choi BS, Choi YJ, Park CW, Kim YS, Cho ML, Yang CW (2011) Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection. Exp Mol Med 43(11):630–637. https://doi.org/10.3858/emm.2011.43.11.071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Holzknecht ZE, Platt JL (2000) The fine cytokine line between graft acceptance and rejection. Nat Med 6(5):497–498. https://doi.org/10.1038/74963

    Article  CAS  PubMed  Google Scholar 

  75. Andreux PA, Houtkooper RH, Auwerx J (2013) Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discov 12(6):465–483. https://doi.org/10.1038/nrd4023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Austin S, St-Pierre J (2012) PGC1α and mitochondrial metabolism–emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci 125(Pt 21):4963–4971. https://doi.org/10.1242/jcs.113662

    Article  CAS  PubMed  Google Scholar 

  77. Breda CNS, Davanzo GG, Basso PJ, Saraiva Câmara NO, Moraes-Vieira PMM (2019) Mitochondria as central hub of the immune system. Redox Biol 26. https://doi.org/10.1016/j.redox.2019.101255

  78. Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116(3):615–622. https://doi.org/10.1172/jci27794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Klotz L, Dani I, Edenhofer F, Nolden L, Evert B, Paul B, Kolanus W, Klockgether T, Knolle P, Diehl L (2007) Peroxisome proliferator-activated receptor gamma control of dendritic cell function contributes to development of CD4+ T cell anergy. J Immunol 178(4):2122–2131. https://doi.org/10.4049/jimmunol.178.4.2122

    Article  CAS  PubMed  Google Scholar 

  80. Weigt SS, Palchevskiy V, Belperio JA (2017) Inflammasomes and IL-1 biology in the pathogenesis of allograft dysfunction. J Clin Invest 127(6):2022–2029. https://doi.org/10.1172/jci93537

    Article  PubMed  PubMed Central  Google Scholar 

  81. de Leur K, Dieterich M, Hesselink DA, Corneth OBJ, Dor F, de Graav GN, Peeters AMA, Mulder A, Kimenai H, Claas FHJ, Clahsen-van Groningen MC, van der Laan LJW, Hendriks RW, Baan CC (2019) Characterization of donor and recipient CD8+ tissue-resident memory T cells in transplant nephrectomies. Sci Rep 9(1):5984. https://doi.org/10.1038/s41598-019-42401-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Kim KW, Kim BM, Doh KC, Cho ML, Yang CW, Chung BH (2018) Clinical significance of CCR7(+)CD8(+) T cells in kidney transplant recipients with allograft rejection. Sci Rep 8(1):8827. https://doi.org/10.1038/s41598-018-27141-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mothe-Satney I, Murdaca J, Sibille B, Rousseau AS, Squillace R, Le Menn G, Rekima A, Larbret F, Pelé J, Verhasselt V, Grimaldi PA, Neels JG (2016) A role for peroxisome proliferator-activated receptor beta in T cell development. Sci Rep 6:34317. https://doi.org/10.1038/srep34317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, Ferris RL, Delgoffe GM (2016) The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction. Immunity 45(2):374–388. https://doi.org/10.1016/j.immuni.2016.07.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, Evans RM (2013) PPARγ signaling and metabolism: the good, the bad and the future. Nat Med 19(5):557–566. https://doi.org/10.1038/nm.3159

    Article  CAS  PubMed  Google Scholar 

  86. Michelet X, Dyck L, Hogan A, Loftus RM, Duquette D, Wei K, Beyaz S, Tavakkoli A, Foley C, Donnelly R, O’Farrelly C, Raverdeau M, Vernon A, Pettee W, O’Shea D, Nikolajczyk BS, Mills KHG, Brenner MB, Finlay D, Lynch L (2018) Metabolic reprogramming of natural killer cells in obesity limits antitumor responses. Nat Immunol 19(12):1330–1340. https://doi.org/10.1038/s41590-018-0251-7

    Article  CAS  PubMed  Google Scholar 

  87. Wahli W, Michalik L (2012) PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab 23(7):351–363. https://doi.org/10.1016/j.tem.2012.05.001

    Article  CAS  PubMed  Google Scholar 

  88. Pearce EJ, Everts B (2015) Dendritic cell metabolism. Nat Rev Immunol 15(1):18–29. https://doi.org/10.1038/nri3771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Zhuang Q, Liu Q, Divito SJ, Zeng Q, Yatim KM, Hughes AD, Rojas-Canales DM, Nakao A, Shufesky WJ, Williams AL, Humar R, Hoffman RA, Shlomchik WD, Oberbarnscheidt MH, Lakkis FG, Morelli AE (2016) Graft-infiltrating host dendritic cells play a key role in organ transplant rejection. Nat Commun 7:12623. https://doi.org/10.1038/ncomms12623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Park H-J, Kim D-H, Choi J-Y, Kim W-J, Kim JY, Senejani AG, Hwang SS, Kim LK, Tobiasova Z, Lee GR, Craft J, Bothwell ALM, Choi J-M (2014) PPARγ negatively regulates T cell activation to prevent follicular helper T cells and germinal center formation. PLoS ONE 9(6):e99127–e99127. https://doi.org/10.1371/journal.pone.0099127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Choi JM, Bothwell AL (2012) The nuclear receptor PPARs as important regulators of T-cell functions and autoimmune diseases. Mol Cells 33(3):217–222. https://doi.org/10.1007/s10059-012-2297-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lee JW, Ko J, Ju C, Eltzschig HK (2019) Hypoxia signaling in human diseases and therapeutic targets. Exp Mol Med 51(6):1–13. https://doi.org/10.1038/s12276-019-0235-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Guak H, Al Habyan S, Ma EH, Aldossary H, Al-Masri M, Won SY, Ying T, Fixman ED, Jones RG, McCaffrey LM, Krawczyk CM (2018) Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration. Nat Commun 9(1):2463. https://doi.org/10.1038/s41467-018-04804-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bernhardt WM, Gottmann U, Doyon F, Buchholz B, Campean V, Schödel J, Reisenbuechler A, Klaus S, Arend M, Flippin L, Willam C, Wiesener MS, Yard B, Warnecke C, Eckardt KU (2009) Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model. Proc Natl Acad Sci USA 106(50):21276–21281. https://doi.org/10.1073/pnas.0903978106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Conde E, Giménez-Moyano S, Martín-Gómez L, Rodríguez M, Ramos ME, Aguado-Fraile E, Blanco-Sanchez I, Saiz A, García-Bermejo ML (2017) HIF-1α induction during reperfusion avoids maladaptive repair after renal ischemia/reperfusion involving miR127-3p. Sci Rep 7(1):41099. https://doi.org/10.1038/srep41099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Schödel J, Ratcliffe PJ (2019) Mechanisms of hypoxia signalling: new implications for nephrology. Nat Rev Nephrol 15(10):641–659. https://doi.org/10.1038/s41581-019-0182-z

    Article  PubMed  Google Scholar 

  97. Parbin S, Kar S, Shilpi A, Sengupta D, Deb M, Rath SK, Patra SK (2014) Histone deacetylases: a saga of perturbed acetylation homeostasis in cancer. J Histochem Cytochem 62(1):11–33. https://doi.org/10.1369/0022155413506582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Kupis W, Pałyga J, Tomal E, Niewiadomska E (2016) The role of sirtuins in cellular homeostasis. J Physiol Biochem 72(3):371–380. https://doi.org/10.1007/s13105-016-0492-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Hayden MS, West AP, Ghosh S (2006) NF-kappaB and the immune response. Oncogene 25(51):6758–6780. https://doi.org/10.1038/sj.onc.1209943

    Article  CAS  PubMed  Google Scholar 

  100. Imai S, Guarente L (2014) NAD+ and sirtuins in aging and disease. Trends Cell Biol 24(8):464–471. https://doi.org/10.1016/j.tcb.2014.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Koyama T, Kume S, Koya D, Araki S, Isshiki K, Chin-Kanasaki M, Sugimoto T, Haneda M, Sugaya T, Kashiwagi A, Maegawa H, Uzu T (2011) SIRT3 attenuates palmitate-induced ROS production and inflammation in proximal tubular cells. Free Radic Biol Med 51(6):1258–1267. https://doi.org/10.1016/j.freeradbiomed.2011.05.028

    Article  CAS  PubMed  Google Scholar 

  102. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. Embo j 23(12):2369–2380. https://doi.org/10.1038/sj.emboj.7600244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Giralt A, Villarroya F (2012) SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging. Biochem J 444(1):1–10. https://doi.org/10.1042/bj20120030

    Article  CAS  PubMed  Google Scholar 

  104. Zhou Q, Lv D, Xia Y, Zhao Z, Zou H (2018) Decreased expression of sirtuin 3 protein correlates with early stage chronic renal allograft dysfunction in a rat kidney model. Exp Ther Med 15(4):3725–3732. https://doi.org/10.3892/etm.2018.5909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Elbe H, Vardi N, Esrefoglu M, Ates B, Yologlu S, Taskapan C (2015) Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats. Hum Exp Toxicol 34(1):100–113. https://doi.org/10.1177/0960327114531995

    Article  CAS  PubMed  Google Scholar 

  106. Hasegawa K, Wakino S, Simic P, Sakamaki Y, Minakuchi H, Fujimura K, Hosoya K, Komatsu M, Kaneko Y, Kanda T, Kubota E, Tokuyama H, Hayashi K, Guarente L, Itoh H (2013) Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes. Nat Med 19(11):1496–1504. https://doi.org/10.1038/nm.3363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Huang K, Huang J, Xie X, Wang S, Chen C, Shen X, Liu P, Huang H (2013) Sirt1 resists advanced glycation end products-induced expressions of fibronectin and TGF-β1 by activating the Nrf2/ARE pathway in glomerular mesangial cells. Free Radic Biol Med 65:528–540. https://doi.org/10.1016/j.freeradbiomed.2013.07.029

    Article  CAS  PubMed  Google Scholar 

  108. Wen D, Huang X, Zhang M, Zhang L, Chen J, Gu Y, Hao CM (2013) Resveratrol attenuates diabetic nephropathy via modulating angiogenesis. PLoS ONE 8(12). https://doi.org/10.1371/journal.pone.0082336

  109. Xu F, Wang Y, Cui W, Yuan H, Sun J, Wu M, Guo Q, Kong L, Wu H, Miao L (2014) Resveratrol prevention of diabetic nephropathy is associated with the suppression of renal inflammation and mesangial cell proliferation: possible roles of Akt/NF-κB pathway. Int J Endocrinol 2014. https://doi.org/10.1155/2014/289327

  110. Gao R, Chen J, Hu Y, Li Z, Wang S, Shetty S, Fu J (2014) Sirt1 deletion leads to enhanced inflammation and aggravates endotoxin-induced acute kidney injury. PLoS ONE 9(6). https://doi.org/10.1371/journal.pone.0098909

  111. Hu M, Wang C, Zhang GY, Saito M, Wang YM, Fernandez MA, Wang Y, Wu H, Hawthorne WJ, Jones C, O’Connell PJ, Sparwasser T, Bishop GA, Sharland AF, Alexander SI (2013) Infiltrating Foxp3(+) regulatory T cells from spontaneously tolerant kidney allografts demonstrate donor-specific tolerance. Am J Transplant 13(11):2819–2830. https://doi.org/10.1111/ajt.12445

    Article  CAS  PubMed  Google Scholar 

  112. Levine MH, Wang Z, Xiao H, Jiao J, Wang L, Bhatti TR, Hancock WW, Beier UH (2016) Targeting Sirtuin-1 prolongs murine renal allograft survival and function. Kidney Int 89(5):1016–1026. https://doi.org/10.1016/j.kint.2015.12.051

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Zhang J, Lee SM, Shannon S, Gao B, Chen W, Chen A, Divekar R, McBurney MW, Braley-Mullen H, Zaghouani H, Fang D (2009) The type III histone deacetylase Sirt1 is essential for maintenance of T cell tolerance in mice. J Clin Invest 119(10):3048–3058. https://doi.org/10.1172/jci38902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Lim HW, Kang SG, Ryu JK, Schilling B, Fei M, Lee IS, Kehasse A, Shirakawa K, Yokoyama M, Schnölzer M, Kasler HG, Kwon HS, Gibson BW, Sato H, Akassoglou K, Xiao C, Littman DR, Ott M, Verdin E (2015) SIRT1 deacetylates RORγt and enhances Th17 cell generation. J Exp Med 212(5):607–617. https://doi.org/10.1084/jem.20132378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Kwon HS, Lim HW, Wu J, Schnölzer M, Verdin E, Ott M (2012) Three novel acetylation sites in the Foxp3 transcription factor regulate the suppressive activity of regulatory T cells. J Immunol 188(6):2712–2721. https://doi.org/10.4049/jimmunol.1100903

    Article  CAS  PubMed  Google Scholar 

  116. Kong S, McBurney MW, Fang D (2012) Sirtuin 1 in immune regulation and autoimmunity. Immunol Cell Biol 90(1):6–13. https://doi.org/10.1038/icb.2011.102

    Article  CAS  PubMed  Google Scholar 

  117. Fairchild RL (2016) Juicing Tregs in situ to improve kidney allograft outcomes. Kidney Int 89(5):976–978. https://doi.org/10.1016/j.kint.2016.01.020

    Article  CAS  PubMed  Google Scholar 

  118. Akimova T, Xiao H, Liu Y, Bhatti TR, Jiao J, Eruslanov E, Singhal S, Wang L, Han R, Zacharia K, Hancock WW, Beier UH (2014) Targeting sirtuin-1 alleviates experimental autoimmune colitis by induction of Foxp3+ T-regulatory cells. Mucosal Immunol 7(5):1209–1220. https://doi.org/10.1038/mi.2014.10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Beier UH, Akimova T, Liu Y, Wang L, Hancock WW (2011) Histone/protein deacetylases control Foxp3 expression and the heat shock response of T-regulatory cells. Curr Opin Immunol 23(5):670–678. https://doi.org/10.1016/j.coi.2011.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Beier UH, Wang L, Han R, Akimova T, Liu Y, Hancock WW (2012) Histone deacetylases 6 and 9 and sirtuin-1 control Foxp3+ regulatory T cell function through shared and isoform-specific mechanisms. Sci Signal 5(229):ra45. https://doi.org/10.1126/scisignal.2002873

  121. Beier UH, Wang L, Bhatti TR, Liu Y, Han R, Ge G, Hancock WW (2011) Sirtuin-1 targeting promotes Foxp3+ T-regulatory cell function and prolongs allograft survival. Mol Cell Biol 31(5):1022–1029. https://doi.org/10.1128/mcb.01206-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Tao R, Hancock WW (2008) Resistance of Foxp3+ regulatory T cells to Nur77-induced apoptosis promotes allograft survival. PLoS ONE 3(5). https://doi.org/10.1371/journal.pone.0002321

  123. Miyajima M, Chase CM, Alessandrini A, Farkash EA, Della Pelle P, Benichou G, Graham JA, Madsen JC, Russell PS, Colvin RB (2011) Early acceptance of renal allografts in mice is dependent on foxp3(+) cells. Am J Pathol 178(4):1635–1645. https://doi.org/10.1016/j.ajpath.2010.12.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Liu P, Huang G, Wei T, Gao J, Huang C, Sun M, Zhu L (1864) Shen W (2018) Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation. Biochim Biophys Acta Mol Basis Dis 3:764–777. https://doi.org/10.1016/j.bbadis.2017.12.027

    Article  CAS  Google Scholar 

  125. Toubai T, Tamaki H, Peltier DC, Rossi C, Oravecz-Wilson K, Liu C, Zajac C, Wu J, Sun Y, Fujiwara H, Henig I, Kim S, Lombard DB, Reddy P (2018) Mitochondrial deacetylase SIRT3 plays an important role in donor T cell responses after experimental allogeneic hematopoietic transplantation. J Immunol 201(11):3443–3455. https://doi.org/10.4049/jimmunol.1800148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Netea MG, Domínguez-Andrés J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E (2020) Defining trained immunity and its role in health and disease. Nat Rev Immunol 20(6):375–388. https://doi.org/10.1038/s41577-020-0285-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Domínguez-Andrés J, Joosten LA, Netea MG (2019) Induction of innate immune memory: the role of cellular metabolism. Curr Opin Immunol 56:10–16. https://doi.org/10.1016/j.coi.2018.09.001

    Article  CAS  PubMed  Google Scholar 

  128. Norata GD, Caligiuri G, Chavakis T, Matarese G, Netea MG, Nicoletti A, O’Neill LA, Marelli-Berg FM (2015) The cellular and molecular basis of translational immunometabolism. Immunity 43(3):421–434. https://doi.org/10.1016/j.immuni.2015.08.023

    Article  CAS  PubMed  Google Scholar 

  129. Penkov S, Mitroulis I, Hajishengallis G, Chavakis T (2019) Immunometabolic crosstalk: an ancestral principle of trained immunity? Trends Immunol 40(1):1–11. https://doi.org/10.1016/j.it.2018.11.002

    Article  CAS  PubMed  Google Scholar 

  130. Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S, Kumar V, Giamarellos-Bourboulis EJ, Martens JH, Rao NA, Aghajanirefah A, Manjeri GR, Li Y, Ifrim DC, Arts RJ, van der Veer BM, Deen PM, Logie C, O’Neill LA, Willems P, van de Veerdonk FL, van der Meer JW, Ng A, Joosten LA, Wijmenga C, Stunnenberg HG, Xavier RJ, Netea MG (2014) mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345(6204):1250684. https://doi.org/10.1126/science.1250684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Donohoe DR, Bultman SJ (2012) Metaboloepigenetics: interrelationships between energy metabolism and epigenetic control of gene expression. J Cell Physiol 227(9):3169–3177. https://doi.org/10.1002/jcp.24054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Cordes T, Wallace M, Michelucci A, Divakaruni AS, Sapcariu SC, Sousa C, Koseki H, Cabrales P, Murphy AN, Hiller K, Metallo CM (2016) Immunoresponsive gene 1 and itaconate inhibit succinate dehydrogenase to modulate intracellular succinate levels. J Biol Chem 291(27):14274–14284. https://doi.org/10.1074/jbc.M115.685792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, Weinheimer CJ, Khader S, Randolph GJ, Pearce EJ, Jones RG, Diwan A, Diamond MS, Artyomov MN (2016) Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab 24(1):158–166. https://doi.org/10.1016/j.cmet.2016.06.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Liu PS, Wang H, Li X, Chao T, Teav T, Christen S, Di Conza G, Cheng WC, Chou CH, Vavakova M, Muret C, Debackere K, Mazzone M, Huang HD, Fendt SM, Ivanisevic J, Ho PC (2017) α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming. Nat Immunol 18(9):985–994. https://doi.org/10.1038/ni.3796

    Article  CAS  PubMed  Google Scholar 

  135. Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, Szpyt J, Runtsch MC, King MS, McGouran JF, Fischer R, Kessler BM, McGettrick AF, Hughes MM, Carroll RG, Booty LM, Knatko EV, Meakin PJ, Ashford MLJ, Modis LK, Brunori G, Sévin DC, Fallon PG, Caldwell ST, Kunji ERS, Chouchani ET, Frezza C, Dinkova-Kostova AT, Hartley RC, Murphy MP, O’Neill LA (2018) Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature 556(7699):113–117. https://doi.org/10.1038/nature25986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Bode K, Bujupi F, Link C, Hein T, Zimmermann S, Peiris D, Jaquet V, Lepenies B, Weyd H, Krammer PH (2019) Dectin-1 binding to annexins on apoptotic cells induces peripheral immune tolerance via NADPH oxidase-2. Cell Rep 29(13):4435-4446.e4439. https://doi.org/10.1016/j.celrep.2019.11.086

    Article  CAS  PubMed  Google Scholar 

  137. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O'Neill LA, Xavier RJ (2016) Trained immunity: a program of innate immune memory in health and disease. Science 352(6284):aaf1098. https://doi.org/10.1126/science.aaf1098

  138. Shen H, Goldstein DR (2009) IL-6 and TNF-alpha synergistically inhibit allograft acceptance. J Am Soc Nephrol 20(5):1032–1040. https://doi.org/10.1681/asn.2008070778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Eckes B, Colucci-Guyon E, Smola H, Nodder S, Babinet C, Krieg T, Martin P (2000) Impaired wound healing in embryonic and adult mice lacking vimentin. J Cell Sci 113(Pt 13):2455–2462

    Article  CAS  PubMed  Google Scholar 

  140. Thiagarajan PS, Yakubenko VP, Elsori DH, Yadav SP, Willard B, Tan CD, Rodriguez ER, Febbraio M, Cathcart MK (2013) Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1. Cardiovasc Res 99(3):494–504. https://doi.org/10.1093/cvr/cvt117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Azimzadeh AM, Pfeiffer S, Wu GS, Schröder C, Zhou H, Zorn GL 3rd, Kehry M, Miller GG, Rose ML, Pierson RN 3rd (2005) Humoral immunity to vimentin is associated with cardiac allograft injury in nonhuman primates. Am J Transplant 5(10):2349–2359. https://doi.org/10.1111/j.1600-6143.2005.01022.x

    Article  CAS  PubMed  Google Scholar 

  142. Braza MS, van Leent MMT, Lameijer M, Sanchez-Gaytan BL, Arts RJW, Pérez-Medina C, Conde P, Garcia MR, Gonzalez-Perez M, Brahmachary M, Fay F, Kluza E, Kossatz S, Dress RJ, Salem F, Rialdi A, Reiner T, Boros P, Strijkers GJ, Calcagno CC, Ginhoux F, Marazzi I, Lutgens E, Nicolaes GAF, Weber C, Swirski FK, Nahrendorf M, Fisher EA, Duivenvoorden R, Fayad ZA, Netea MG, Mulder WJM, Ochando J (2018) Inhibiting inflammation with myeloid cell-specific nanobiologics promotes organ transplant acceptance. Immunity 49(5):819-828.e816. https://doi.org/10.1016/j.immuni.2018.09.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Miller LW, Granville DJ, Narula J, McManus BM (2001) Apoptosis in cardiac transplant rejection. Cardiol Clin 19(1):141–154. https://doi.org/10.1016/s0733-8651(05)70200-9

    Article  CAS  PubMed  Google Scholar 

  144. Rose ML (2004) De novo production of antibodies after heart or lung transplantation should be regarded as an early warning system. J Heart Lung Transplant 23(4):385–395. https://doi.org/10.1016/j.healun.2003.08.028

    Article  PubMed  Google Scholar 

  145. Linkermann A, Bräsen JH, Darding M, Jin MK, Sanz AB, Heller JO, De Zen F, Weinlich R, Ortiz A, Walczak H, Weinberg JM, Green DR, Kunzendorf U, Krautwald S (2013) Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proc Natl Acad Sci USA 110(29):12024–12029. https://doi.org/10.1073/pnas.1305538110

    Article  PubMed  PubMed Central  Google Scholar 

  146. Huang Y, Yin H, Han J, Huang B, Xu J, Zheng F, Tan Z, Fang M, Rui L, Chen D, Wang S, Zheng X, Wang CY, Gong F (2007) Extracellular hmgb1 functions as an innate immune-mediator implicated in murine cardiac allograft acute rejection. Am J Transplant 7(4):799–808. https://doi.org/10.1111/j.1600-6143.2007.01734.x

    Article  CAS  PubMed  Google Scholar 

  147. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418(6894):191–195. https://doi.org/10.1038/nature00858

    Article  CAS  PubMed  Google Scholar 

  148. Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, Chadban SJ (2010) HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol 21(11):1878–1890. https://doi.org/10.1681/asn.2009101048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, Philpott DJ, Sansonetti PJ (2003) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278(11):8869–8872. https://doi.org/10.1074/jbc.C200651200

    Article  CAS  PubMed  Google Scholar 

  150. Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (2009) Activation of innate immune antiviral responses by Nod2. Nat Immunol 10(10):1073–1080. https://doi.org/10.1038/ni.1782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Chong AS, Alegre ML (2012) The impact of infection and tissue damage in solid-organ transplantation. Nat Rev Immunol 12(6):459–471. https://doi.org/10.1038/nri3215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Martin-Gandul C, Mueller NJ, Pascual M, Manuel O (2015) The impact of infection on chronic allograft dysfunction and allograft survival after solid organ transplantation. Am J Transplant 15(12):3024–3040. https://doi.org/10.1111/ajt.13486

    Article  CAS  PubMed  Google Scholar 

  153. Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG (2012) Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A 109(43):17537–17542. https://doi.org/10.1073/pnas.1202870109

    Article  PubMed  PubMed Central  Google Scholar 

  154. Mulder WJM, Ochando J, Joosten LAB, Fayad ZA, Netea MG (2019) Therapeutic targeting of trained immunity. Nat Rev Drug Discov 18(7):553–566. https://doi.org/10.1038/s41573-019-0025-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Tabibian JH, Kenderian SS (2017) The microbiome and immune regulation after transplantation. Transplantation 101(1):56–62. https://doi.org/10.1097/tp.0000000000001444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9(5):313–323. https://doi.org/10.1038/nri2515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Thaiss CA, Zmora N, Levy M, Elinav E (2016) The microbiome and innate immunity. Nature 535(7610):65–74. https://doi.org/10.1038/nature18847

    Article  CAS  PubMed  Google Scholar 

  158. Kim CH (2018) Immune regulation by microbiome metabolites. Immunology 154(2):220–229. https://doi.org/10.1111/imm.12930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453(7191):65–71. https://doi.org/10.1038/nature06880

    Article  CAS  PubMed  Google Scholar 

  160. Goudot C, Coillard A, Villani AC, Gueguen P, Cros A, Sarkizova S, Tang-Huau TL, Bohec M, Baulande S, Hacohen N, Amigorena S, Segura E (2017) Aryl hydrocarbon receptor controls monocyte differentiation into dendritic cells versus macrophages. Immunity 47(3):582-596.e586. https://doi.org/10.1016/j.immuni.2017.08.016

    Article  CAS  PubMed  Google Scholar 

  161. Singh NP, Singh UP, Rouse M, Zhang J, Chatterjee S, Nagarkatti PS, Nagarkatti M (2016) Dietary indoles suppress delayed-type hypersensitivity by inducing a switch from proinflammatory Th17 cells to anti-inflammatory regulatory T cells through regulation of microRNA. J Immunol 196(3):1108–1122. https://doi.org/10.4049/jimmunol.1501727

    Article  CAS  PubMed  Google Scholar 

  162. Levy M, Thaiss CA, Elinav E (2016) Metabolites: messengers between the microbiota and the immune system. Genes Dev 30(14):1589–1597. https://doi.org/10.1101/gad.284091.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40(1):128–139. https://doi.org/10.1016/j.immuni.2013.12.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Haase S, Haghikia A, Wilck N, Müller DN, Linker RA (2018) Impacts of microbiome metabolites on immune regulation and autoimmunity. Immunology 154(2):230–238. https://doi.org/10.1111/imm.12933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Nastasi C, Candela M, Bonefeld CM, Geisler C, Hansen M, Krejsgaard T, Biagi E, Andersen MH, Brigidi P, Ødum N, Litman T, Woetmann A (2015) The effect of short-chain fatty acids on human monocyte-derived dendritic cells. Sci Rep 5:16148. https://doi.org/10.1038/srep16148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Dery KJ, Kadono K, Hirao H, Górski A, Kupiec-Weglinski JW (2020) Microbiota in organ transplantation: an immunological and therapeutic conundrum? Cell Immunol 351. https://doi.org/10.1016/j.cellimm.2020.104080

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Niels Olsen Saraiva Camara .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Domínguez-Amorocho, O., De Lima, J., Camara, N.O.S. (2022). Immunometabolism and Organ Transplantation. In: Camara, N.O.S., Alves-Filho, J.C., Moraes-Vieira, P.M.M.d., Andrade-Oliveira, V. (eds) Essential Aspects of Immunometabolism in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-86684-6_13

Download citation

Publish with us

Policies and ethics