Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Front Immunol. 2020 Oct 14;11:582658. doi: 10.3389/fimmu.2020.582658. eCollection 2020.
Current organ transplantation therapy is life-saving but accompanied by well-recognized side effects due to post-transplantation systematic immunosuppressive treatment. Dendritic cells (DCs) are central instigators and regulators of transplantation immunity and are responsible for balancing allograft rejection and tolerance. They are derived from monocyte-macrophage DC progenitors originating in the bone marrow and are classified into different subsets based on their developmental, phenotypical, and functional criteria. Functionally, DCs instigate allograft immunity by presenting donor antigens to alloreactive T cells via direct, indirect, and semidirect recognition pathways and provide essential signaling for alloreactive T cell activation via costimulatory molecules and pro-inflammatory cytokines. Regulatory DCs (DCregs) are characterized by a relatively low expression of major histocompatibility complex, costimulatory molecules, and altered cytokine production and exert their regulatory function through T cell anergy, T cell deletion, and regulatory T cell induction. In rodent transplantation studies, DCreg-based therapy, by targeting or infusion of generated DCregs, exhibits promising potential as a natural, well-tolerated, organ-specific therapeutic strategy for promoting lasting organ-specific transplantation tolerance. Recent early-phase studies of DCregs have begun to examine the safety and efficacy of DCreg-induced allograft tolerance in living-donor renal or liver transplantations. The present review summarizes the basic characteristics, function, and translation of DCregs in transplantation tolerance induction.
目前的器官移植治疗是救命的，但由于移植后系统性免疫抑制治疗，会伴随公认的副作用。树突状细胞（DCs）是移植免疫的主要启动者和调节者，负责平衡同种异体移植物排斥和耐受。它们来源于骨髓中的单核细胞-巨噬细胞 DC 前体，并根据其发育、表型和功能标准分为不同的亚群。在功能上，DCs 通过直接、间接和半间接识别途径将供体抗原呈递给同种反应性 T 细胞，通过共刺激分子和促炎细胞因子为同种反应性 T 细胞激活提供必需的信号。调节性 DCs（DCregs）的特征是主要组织相容性复合体、共刺激分子的表达相对较低，以及细胞因子产生的改变，并通过 T 细胞无能、T 细胞删除和调节性 T 细胞诱导发挥其调节功能。在啮齿动物移植研究中，基于 DCreg 的治疗通过靶向或输注生成的 DCregs，作为一种自然的、耐受良好的、器官特异性的治疗策略，具有促进持久的器官特异性移植耐受的巨大潜力。最近对 DCregs 的早期研究开始检查 DCreg 诱导的同种异体移植物耐受在活体供肾或肝移植中的安全性和疗效。本综述总结了 DCregs 在移植耐受诱导中的基本特征、功能和转化。
