Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, Nagakute, Japan.
Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
Front Immunol. 2022 Mar 28;13:858604. doi: 10.3389/fimmu.2022.858604. eCollection 2022.
Xenotransplantation is very attractive strategy for addressing the shortage of donors. While hyper acute rejection (HAR) caused by natural antibodies and complement has been well defined, this is not the case for innate cellular xenogeneic rejection. An increasing body of evidence suggests that innate cellular immune responses contribute to xenogeneic rejection. Various molecular incompatibilities between receptors and their ligands across different species typically have an impact on graft outcome. NK cells are activated by direct interaction as well as by antigen dependent cellular cytotoxicity (ADCC) mechanisms. Macrophages are activated through various mechanisms in xenogeneic conditions. Macrophages recognize CD47 as a "marker of self" through binding to SIRPα. A number of studies have shown that incompatibility of porcine CD47 against human SIRPα contributes to the rejection of xenogeneic target cells by macrophages. Neutrophils are an early responder cell that infiltrates xenogeneic grafts. It has also been reported that neutrophil extracellular traps (NETs) activate macrophages as damage-associated pattern molecules (DAMPs). In this review, we summarize recent insights into innate cellular xenogeneic rejection.
异种移植是解决供体短缺的一种非常有吸引力的策略。虽然由天然抗体和补体引起的超急性排斥反应（HAR）已经得到了很好的定义，但对于固有细胞异种排斥反应则并非如此。越来越多的证据表明，固有细胞免疫反应有助于异种排斥反应。不同物种之间受体与其配体之间的各种分子不兼容性通常会影响移植物的结果。NK 细胞通过直接相互作用以及抗原依赖性细胞毒性（ADCC）机制被激活。巨噬细胞在异种条件下通过各种机制被激活。巨噬细胞通过与 SIRPα 结合识别 CD47 作为“自身标志物”。许多研究表明，猪 CD47 与人类 SIRPα 的不兼容性导致巨噬细胞排斥异种靶细胞。中性粒细胞是浸润异种移植物的早期反应细胞。据报道，中性粒细胞胞外诱捕网（NETs）作为损伤相关模式分子（DAMPs）激活巨噬细胞。在这篇综述中，我们总结了固有细胞异种排斥反应的最新研究进展。
