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Tregs and kidney: From diabetic nephropathy to renal transplantation

机译:Tregs和肾脏:从糖尿病肾病到肾脏移植

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摘要

Kidney transplantation is recognised as the most effective treatment for patients with end-stage renal disease (ESRD). Kidney transplantation continues to face several challenges including long-term graft and patient survival, and the side effects of immunosuppressive therapy. The tendency in kidney transplantation is to avoid the side effects of immunosuppresants and induce immune tolerance. Regulatory T-cells (Tregs) contribute to self-tolerance, tolerance to alloantigen and transplant tolerance, mainly by suppressing the activation and function of reactive effector T-cells. Additionally, Tregs are implicated in the pathogenesis of diabetes, which is the leading cause of ESRD, suggesting that these cells play a role both in the pathogenesis of chronic kidney disease and the induction of transplant tolerance. Several strategies to achieve immunological tolerance to grafts have been tested experimentally, and include combinations of co-stimulatory blockade pathways, T-cell depletion, in vivo Treg-induction and/or infusion of ex-vivo expanded Tregs. However, a successful regimen that induces transplant tolerance is not yet available for clinical application. This review brings together certain key studies on the role of Tregs in ESRD, diabetes and kidney transplantation, only to emphasize that many more studies are needed to elucidate the clinical significance and the therapeutic applications of Tregs.
机译:肾移植被认为是晚期肾病(ESRD)患者的最有效治疗方法。肾脏移植继续面临一些挑战,包括长期移植和患者生存以及免疫抑制疗法的副作用。肾脏移植的趋势是避免免疫抑制剂的副作用并诱导免疫耐受。调节性T细胞(Tregs)主要通过抑制反应性效应T细胞的激活和功能来促进自身耐受性,对同种抗原的耐受性和移植耐受性。另外,Tregs参与糖尿病的发病机理,这是ESRD的主要原因,提示这些细胞在慢性肾脏疾病的发病机理和诱导移植耐受中均起着作用。已通过实验测试了几种实现对移植物免疫耐受的策略,包括共同刺激性阻断途径,T细胞耗竭,体内Treg诱导和/或输注体外Treg的组合。但是,诱导移植耐受的成功方案尚不能用于临床。这篇综述汇集了关于Tregs在ESRD,糖尿病和肾脏移植中作用的某些关键研究,只是强调需要更多的研究来阐明Tregs的临床意义和治疗应用。

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