Trained immunity suppression determines kidney allograft survival.

Autor:	Jonkman I; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Jacobs MME; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Negishi Y; Department of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands., Yanginlar C; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Martens JHA; Department of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands., Baltissen M; Department of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands., Vermeulen M; Department of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands., van den Hoogen MWF; Department of Internal Medicine, Erasmus Medical Center Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands., Baas M; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., van der Vlag J; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Fayad ZA; Department of Radiology, Biomolecular Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Teunissen AJP; Department of Radiology, Biomolecular Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Madsen JC; Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts, USA; Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA., Ochando J; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Transplant Immunology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain., Joosten LAB; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Genetics, University of Medicine and Pharmacy, Iuliu Haţieganu, Cluj-Napoca, Romania., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany., Mulder WJM; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Biomedical Engineering and Institute for Complex Molecular Systems, Laboratory of Chemical Biology, Eindhoven University of Technology, Eindhoven, The Netherlands., Mhlanga MM; Department of Molecular Biology, Faculty of Science, Oncode Institute, Radboud University Nijmegen, Nijmegen, The Netherlands; Department of Cell Biology, Faculty of Science, Radboud University Nijmegen, Nijmegen, The Netherlands., Hilbrands LB; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Rother N; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., Duivenvoorden R; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiology, Biomolecular Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: raphael.duivenvoorden@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2024 Nov; Vol. 24 (11), pp. 2022-2033. Date of Electronic Publication: 2024 Aug 13.
DOI:	10.1016/j.ajt.2024.08.006
Abstrakt:	The innate immune system plays an essential role in regulating the immune responses to kidney transplantation, but the mechanisms through which innate immune cells influence long-term graft survival are unclear. The current study highlights the vital role of trained immunity in kidney allograft survival. Trained immunity describes the epigenetic and metabolic changes that innate immune cells undergo following an initial stimulus, allowing them have a stronger inflammatory response to subsequent stimuli. We stimulated healthy peripheral blood mononuclear cells with pretransplant and posttransplant serum of kidney transplant patients and immunosuppressive drugs in an in vitro trained immunity assay and measured tumor necrosis factor and interleukin 6 cytokine levels in the supernatant as a readout for trained immunity. We show that the serum of kidney transplant recipients collected 1 week after transplantation can suppress trained immunity. Importantly, we found that kidney transplant recipients whose serum most strongly suppressed trained immunity rarely experienced graft loss. This suppressive effect of posttransplant serum is likely mediated by previously unreported effects of immunosuppressive drugs. Our findings provide mechanistic insights into the role of innate immunity in kidney allograft survival, uncovering trained immunity as a potential therapeutic target for improving graft survival. Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. L. A. B. Joosten is scientific founder of TTxD, LembaTX, and SalvinaTX. M. G. Netea is scientific founder of TTxD and Biotrip. W. J. M. Mulder is scientific founder of TTxD and Biotrip. Other authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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