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Natural Killer Cells in Kidney Transplantation: Dual Role in Allograft Injury and Immune Adaptation Cover

Natural Killer Cells in Kidney Transplantation: Dual Role in Allograft Injury and Immune Adaptation

Open Access
|Sep 2026

References

  1. Alari-Pahissa E, Federico-Vega J, Ataya M et al. (2025) Alloreactive adaptive natural killer cells in renal transplantation: potential con-tribution to allograft microvascular inflammation. Am J Transplant 25:1657–1669. https://doi.org/10.1016/j.ajt.2025.04.024
  2. Ashraf MI, Sarwar A, Kühl AA et al. (2019) Natural killer cells pro-mote kidney graft rejection independently of cyclosporine a therapy. Front Immunol 10:2279. https://doi.org/10.3389/fimmu.2019.02279
  3. Ataya M, Redondo-Pachón D, Llinàs-Mallol L et al. (2020) Pretransplant adaptive NKG2C+ NK cells protect against cyto-megalovirus infection in kidney transplant recipients. Am J Transplant 20:663–676. https://doi.org/10.1111/ajt.15658
  4. Babich T, Daitch V, Leibovici L et al. (2026) Life expectancy after kidney transplantation in a population-based retro-spective cohort. Sci Rep 16:6310. https://doi.org/10.1038/s41598-026-37536-5
  5. Bielekova B, Catalfamo M, Reichert-Scrivner S et al. (2006) Regulatory CD56(bright) natural killer cells mediate immuno-modulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci USA 103:5941–5946. https://doi.org/10.1073/pnas.0601335103
  6. Clatworthy MR (2011) Targeting B cells and antibody in trans-plantation. Am J Transplant 11:1359–1367. https://doi.org/10.1111/j.1600-6143.2011.03554.x
  7. Delville M, Charreau B, Rabant M et al. (2016) Pathogenesis of non-HLA antibodies in solid organ transplantation: where do we stand? Hum Immunol 77:1055–1062. https://doi.org/10.1016/j.humimm.2016.05.021
  8. Diebold M, Mayer KA, Hidalgo L et al. (2025) Chronic rejection after kidney transplantation. Transplantation 109:610–621. https://doi.org/10.1097/TP.0000000000005187
  9. Foley B, Cooley S, Verneris MR et al. (2011) NK cell education after allogeneic transplantation: dissociation between recovery of cytokine-producing and cytotoxic functions. Blood 118:2784–2792. https://doi.org/10.1182/blood-2011-04-347070
  10. Fuhrmann B, Jiang J, Mcleod P et al. (2024) Inhibition of NK cell cytotoxicity by tubular epithelial cell expression of Clr-b and Clr-f. Curr Res Immunol 5:100081. https://doi.org/10.1016/j.crimmu.2024.100081
  11. Ghasemzadeh M, Hosseini E, Schwarer AP et al. (2016) NK cell maturation to CD56(dim) subset associated with high levels of NCRs overrides the inhibitory effect of NKG2A and recovers impaired NK cell cytolytic potential after allogeneic hematopoi-etic stem cell transplantation. Leuk Res 43:58–65. https://doi.org/10.1016/j.leukres.2015.12.002
  12. Gumá M, Angulo A, Vilches C et al. (2004) Imprint of human cyto-megalovirus infection on the NK cell receptor repertoire. Blood 104:3664–3671. https://doi.org/10.1182/blood-2004-05-2058
  13. Hadaya K, de Rham C, Bandelier C et al. (2008) Natural killer cell receptor repertoire and their ligands, and the risk of CMV infec-tion after kidney transplantation. Am J Transplant 8:2674–2683. https://doi.org/10.1111/j.1600-6143.2008.02431.x
  14. Halloran PF (2010) T cell-mediated rejection of kidney transplants: a personal viewpoint. Am J Transplant 10:1126–1134. https://doi.org/10.1111/j.1600-6143.2010.03053.x
  15. Hassan N, Eldershaw S, Stephens C et al. (2022) CMV reactivation initiates long-term expansion and differentiation of the NK cell repertoire. Front Immunol 13:935949. https://doi.org/10.3389/fimmu.2022.935949
  16. Hiura S, Kuwasaki Y, Nishikawa Y et al. (2025) Selective ago-nists of KIR and NKG2A to evade missing self response of natural killer cells. Sci Rep 15:33550. https://doi.org/10.1038/s41598-025-18394-z
  17. Horowitz A, Heeger P (2026) Natural killer cells in kidney immune surveillance, injury and fibrosis. Nat Rev Nephrol 22:215–228. https://doi.org/10.1038/s41581-025-01029-x
  18. Hosseini E, Minagar A, Ghasemzadeh M et al. (2023) HLA-E*01:01 + HLA-E*01:01 genotype confers less susceptibility to COVID-19, while HLA-E*01:03 + HLA-E*01:03 genotype is associated with more severe disease. Hum Immunol 84:263–271. https://doi.org/10.1016/j.humimm.2023.02.002
  19. Hosseini E, Schwarer AP, Jalali A et al. (2013) The impact of HLA-E polymorphisms on relapse following allogeneic hematopoietic stem cell transplantation. Leuk Res 37:516–519. https://doi.org/10.1016/j.leukres.2013.01.011
  20. Kaulfuss M, Mietz J, Fabri A et al. (2023) The NK cell checkpoint NKG2A maintains expansion capacity of human NK cells. Sci Rep 13:10555. https://doi.org/10.1038/s41598-023-37779-6
  21. Kildey K, Francis RS, Hultin S et al. (2019) Specialized roles of human natural killer cell subsets in kidney transplant rejection. Front Immunol 10:1877. https://doi.org/10.3389/fimmu.2019.01877
  22. Le Garff-Tavernier M, Decocq J, de Romeuf C et al. (2011) Analysis of CD16+CD56dim NK cells from CLL patients: evidence sup-porting a therapeutic strategy with optimized anti-CD20 monoclo-nal antibodies. Leukemia 25:101–109. https://doi.org/10.1038/leu.2010.240
  23. Lebraud E, Eloudzeri M, Rabant M et al. (2022) Microvascular inflammation of the renal allograft: a reappraisal of the underlying mechanisms. Front Immunol 13:864730. https://doi.org/10.3389/fimmu.2022.864730
  24. Mahr B, Pilat N, Maschke S et al. (2017) Regulatory T cells promote natural killer cell education in mixed chimeras. Am J Transplant 17:3049–3059. https://doi.org/10.1111/ajt.14342
  25. Ma K, Zheng Z-R, Meng Y (2023) Natural killer cells, as the rising point in tissues, are forgotten in the kidney. Biomolecules 13:748. https://doi.org/10.3390/biom13050748
  26. Meier-Kriesche HU, Ojo AO, Port FK et al. (2001) Survival improve-ment among patients with end-stage renal disease: trends over time for transplant recipients and wait-listed patients. J Am Soc Nephrol 12:1293–1296. https://doi.org/10.1681/ASN.V1261293
  27. Moroso V, Metselaar HJ, Mancham S et al. (2010) Liver grafts contain a unique subset of natural killer cells that are transferred into the recipient after liver transplantation. Liver Transpl 16:895–908. https://doi.org/10.1002/lt.22080
  28. Paul S, Lal G (2017) The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front Immunol 8:1124. https://doi.org/10.3389/fimmu.2017.01124
  29. Poggio ED, Augustine JJ, Arrigain S et al. (2021) Long-term kidney transplant graft survival-making progress when most needed. Am J Transplant 21:2824–2832. https://doi.org/10.1111/ajt.16463
  30. Poli A, Michel T, Thérésine M et al. (2009) CD56bright natural killer (NK) cells: an important NK cell subset. Immunology 126:458–465. https://doi.org/10.1111/j.1365-2567.2008.03027.x
  31. Pontrelli P, Rascio F, Castellano G et al. (2020) The role of natural killer cells in the immune response in kidney transplantation. Front Immunol 11:1454. https://doi.org/10.3389/fimmu.2020.01454
  32. Qin R, Qin J, Li X et al. (2023) Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation. Hepatobiliary Surg Nutr 12:835–853. https://doi.org/10.21037/hbsn-22-438
  33. Ruan DF, Fribourg M, Yuki Y et al. (2024) High-dimensional analysis of NK cells in kidney transplantation uncovers subsets associ-ated with antibody-independent graft dysfunction. JCI Insight 9:e185687. https://doi.org/10.1172/jci.insight.185687
  34. Schlums H, Cichocki F, Tesi B et al. (2015) Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function. Immunity 42:443–456. https://doi.org/10.1016/j.immuni.2015.02.008
  35. Troise D, Infante B, Mercuri S et al. (2025) Exploring the immunologi-cal landscape of ischemia/reperfusion injury and graft rejection in kidney transplantation: shared mechanisms and insights. Cells 14:1443. https://doi.org/10.3390/cells14181443
  36. Tsao T, Qiu L, Bharti R (2024) CD94+ natural killer cells potentiate pul-monary ischaemia-reperfusion injury. Eur Respir J 64:2302171. https://doi.org/10.1183/13993003.02171-2023
  37. Van Acker HH, Capsomidis A, Smits EL et al. (2017) CD56 in the immune system: more than a marker for cytotoxicity? Front Immunol 8:892. https://doi.org/10.3389/fimmu.2017.00892
  38. Xu X, Han Y, Huang H et al. (2019) Circulating NK cell subsets and NKT like cells in renal transplant recipients with acute T cell mediated renal allograft rejection. Mol Med Rep 19:4238–4248. https://doi.org/10.3892/mmr.2019.10091
  39. Yu G, Xu X, Vu MD et al. (2006) NK cells promote transplant tol-erance by killing donor antigen-presenting cells. J Exp Med 203:1851–1858. https://doi.org/10.1084/jem.20060603
  40. Zagorulya M, Yim L, Morgan DM et al. (2023) Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer. Immunity 56:386–405.e10. https://doi.org/10.1016/j.immuni.2023.01.010
Language: English
Submitted on: May 30, 2026
Accepted on: Aug 7, 2026
Published on: Sep 30, 2026
Published by: Hirszfeld Institute of Immunology and Experimental Therapy
In partnership with: Paradigm Publishing Services
Publication frequency: 1 issue per year

© 2026 Anna Skotny, Paweł Poznański, Katarzyna Kościelska-Kasprzak, Dorota Bartoszek, Marcelina Żabińska, Dorota Kamińska, Magdalena Krajewska, published by Hirszfeld Institute of Immunology and Experimental Therapy
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.