Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Front Immunol. 2019 Dec 19;10:2978. doi: 10.3389/fimmu.2019.02978. eCollection 2019.
Over the last decades, our understanding of adaptive immune responses to solid organ transplantation increased considerably and allowed development of immunosuppressive drugs targeting key alloreactive T cells mechanism. As a result, rates of acute rejection dropped and short-term graft survival improved significantly. However, long-term outcomes are still disappointing. Recently, increasing evidence supports that innate immune responses plays roles in allograft rejection and represents a valuable target to further improve long-term allograft survival. Innate immune cells are activated by molecules with stereotypical motifs produced during injury (i.e., damage-associated molecular patterns, DAMPS) or infection (i.e., pathogen-associated molecular patterns, PAMPs). Activated innate immune cells can exert direct pro- and anti-inflammatory effects, while also priming adaptive immune responses. These cells are activated after transplantation by multiple stimuli, including ischemia-reperfusion injury, rejection, and infections. Data from animal models of graft rejection, show that inhibition of innate immunity promotes development of tolerance. Therefore, understanding mechanisms of innate immunity is important to improve graft outcomes. This review discusses effects of currently used immunosuppressive agents on innate immune responses in kidney transplantation.
在过去的几十年中，我们对实体器官移植中适应性免疫反应的理解有了很大的提高，并开发了针对关键同种异体反应性 T 细胞机制的免疫抑制药物。结果，急性排斥反应的发生率下降，短期移植物存活率显著提高。然而，长期结果仍然令人失望。最近，越来越多的证据支持先天免疫反应在同种异体移植物排斥中起作用，并代表了进一步提高长期移植物存活率的有价值的目标。先天免疫细胞被损伤过程中产生的具有典型基序的分子（即损伤相关分子模式，DAMPS）或感染（即病原体相关分子模式，PAMPs）激活。激活的先天免疫细胞可以发挥直接的促炎和抗炎作用，同时也启动适应性免疫反应。这些细胞在移植后会被多种刺激激活，包括缺血再灌注损伤、排斥和感染。来自移植物排斥动物模型的数据表明，先天免疫抑制可促进耐受的发展。因此，了解先天免疫的机制对于改善移植物的结果很重要。本文综述了目前用于肾移植的免疫抑制剂对先天免疫反应的影响。
