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.

中文翻译：

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训练有素的免疫抑制决定移植肾的存活率


先天免疫系统在调节对肾移植的免疫反应中起着至关重要的作用，但先天免疫细胞影响移植物长期存活的机制尚不清楚。目前的研究强调了训练有素的免疫力在同种异体肾移植物存活中的重要作用。训练有素的免疫力描述了先天免疫细胞在初始刺激后经历的表观遗传和代谢变化，使它们对后续刺激具有更强的炎症反应。我们在体外训练的免疫测定中用肾移植患者移植前和移植后血清和免疫抑制药物刺激健康的外周血单核细胞，并测量上清液中的肿瘤坏死因子和白细胞介素 6 细胞因子水平作为训练免疫力的读数。我们表明，移植后 1 周收集的肾移植受者的血清可以抑制训练有素的免疫力。重要的是，我们发现血清最强烈抑制训练免疫力的肾移植受者很少出现移植物丢失。移植后血清的这种抑制作用可能是由先前未报道的免疫抑制药物作用介导的。我们的研究结果为先天免疫在同种异体肾移植物存活中的作用提供了机制见解，揭示了训练有素的免疫力作为提高移植物存活率的潜在治疗靶点。