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oai:repisalud.isciii.es:20.500.12105/123902024-09-27T20:38:22Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Ochando, Jordi author Fayad, Zahi A author Madsen, Joren C author Netea, Mihai G author Mulder, Willem J M author 2020 Consistent induction of donor-specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen-presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long-term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro-inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection. Am J Transplant. 2020 Jan;20(1):10-18. http://hdl.handle.net/20.500.12105/12390 31561273 10.1111/ajt.15620 1600-6143 American journal of transplantation: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Trained immunity in organ transplantation.