Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Immunología de Trasplantes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
Cell Mol Immunol. 2019 Apr;16(4):350-356. doi: 10.1038/s41423-019-0216-2. Epub 2019 Feb 25.
Surgical trauma and ischemia reperfusion injury (IRI) are unavoidable aspects of any solid organ transplant procedure. They trigger a multifactorial antigen-independent inflammatory process that profoundly affects both the early and long-term outcomes of the transplanted organ. The injury associated with donor organ procurement, storage, and engraftment triggers innate immune activation that inevitably results in cell death, which may occur in many different forms. Dying cells in donor grafts release damage-associated molecular patterns (DAMPs), which alert recipient innate cells, including macrophages and dendritic cells (DCs), through the activation of the complement cascade and toll-like receptors (TLRs). The long-term effect of inflammation on innate immune cells is associated with changes in cellular metabolism that skew the cells towards aerobic glycolysis, resulting in innate immune cell activation and inflammatory cytokine production. The different roles of proinflammatory cytokines in innate immune activation have been described, and these cytokines also stimulate optimal T-cell expansion during allograft rejection. Therefore, early innate immune events after organ transplantation determine the fate of the adaptive immune response. In this review, we summarize the contributions of innate immunity to allograft rejection and discuss recent studies and emerging concepts in the targeted delivery of therapeutics to modulate the innate immune system to enhance allograft survival.
手术创伤和缺血再灌注损伤（IRI）是任何实体器官移植过程中不可避免的方面。它们引发了一种多因素的、非抗原依赖性的炎症过程，对移植器官的早期和长期结果都有深远的影响。与供体器官获取、储存和植入相关的损伤会触发先天免疫激活，不可避免地导致细胞死亡，而细胞死亡可能以多种不同的形式发生。供体移植物中死亡的细胞释放损伤相关分子模式（DAMPs），通过补体级联和 Toll 样受体（TLRs）的激活，向包括巨噬细胞和树突状细胞（DC）在内的受体内在细胞发出警报。炎症对固有免疫细胞的长期影响与细胞代谢的变化有关，这种变化使细胞偏向于有氧糖酵解，导致固有免疫细胞的激活和炎症细胞因子的产生。促炎细胞因子在固有免疫激活中的不同作用已经被描述过，这些细胞因子也在同种异体移植排斥反应中刺激最佳的 T 细胞扩增。因此，器官移植后早期的固有免疫事件决定了适应性免疫反应的命运。在这篇综述中，我们总结了固有免疫对同种异体移植排斥的贡献，并讨论了最近在靶向传递治疗药物以调节固有免疫系统以增强同种异体移植物存活方面的研究和新兴概念。
