《生命科学》 2026, 38(4): 721-735

树突状细胞在肝移植免疫中的双重作用及其临床转化进展

杜 利¹ , 刘方方² , 何俊明³ , 王闻雅^1,*

¹清华大学北京清华长庚医院临床药械试验中心，北京 102218 ²吉林市中心医院神经内科，吉林 132011 ³清华大学北京清华长庚医院器官移植与仿生医学科学研究中心，北京 102218

摘　要：

肝移植（LT）是终末期肝病的有效治疗手段，但长期免疫抑制剂的应用仍带来感染、代谢紊乱等不良反应，限制了临床获益。树突状细胞（DCs）作为连接先天与适应性免疫的关键细胞，在LT中发挥免疫激活与免疫耐受的双重作用：一方面通过抗原呈递启动同种异体免疫反应，介导移植排斥；另一方面在特定微环境下诱导免疫耐受，参与移植物长期存活。本文围绕抗原识别通路、肝脏免疫微环境及免疫代谢重编程，系统综述DCs在LT中的功能调控机制。研究表明，糖酵解促进DCs向免疫原性表型分化，而脂肪酸氧化及氧化磷酸化有助于维持其耐受性表型（tolDCs）。在临床转化方面，基于tolDCs的细胞治疗及体内靶向调控策略已显示出诱导免疫耐受的潜力，但其表型稳定性及与现有免疫抑制治疗的协同机制仍有待进一步研究。未来，结合多组学技术构建DCs相关免疫评估体系，有望推动肝移植从非特异性免疫抑制向精准免疫调控转变。

通讯作者：王闻雅 , Email:wwya03378@btch.edu.cn

Dual roles of dendritic cells in liver transplantation immunity and their translational progress

DU Li¹ , LIU Fang-Fang² , HE Jun-Ming³ , WANG Wen-Ya^1,*

¹Clinical Trial Center for Drugs and Medical Devices, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China ²Department of Neurology, Jilin Central General Hospital, Jilin 132011, China ³Science Research Center for Institute for Organ Transplant and Bionic Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China

Abstract:

Liver transplantation (LT) remains the definitive treatment for end-stage liver disease; however, its long-term success is limited by the lifelong dependence on immunosuppressive therapy and its associated complications. Dendritic cells (DCs), as key orchestrators bridging innate and adaptive immunity, play a dual and paradoxical role in LT by simultaneously driving allograft rejection and promoting immune tolerance. This review provides a comprehensive synthesis of DCs immunobiology in LT, with a focus on their functional heterogeneity, spatial distribution, and dynamic fate determination. We first summarize the three principal DCs-mediated allorecognition pathways—direct, indirect, and semi-direct—and highlight their temporal interplay across different transplantation stages. Notably, the semi-direct pathway, characterized by “crossdressing”of recipient DCs with intact donor MHC complexes, emerges as a critical mechanism for immune regulation and tolerance induction within the unique hepatic microenvironment. A central concept of this review is that immunometabolic reprogramming governs DCs functional fate. Immunogenic DCs predominantly rely on glycolysis to support rapid activation and pro-inflammatory responses, whereas tolerogenic DCs (tolDCs) preferentially utilize oxidative phosphorylation and fatty acid oxidation to maintain their regulatory phenotype. This metabolic dichotomy functions as a molecular switch that integrates environmental cues—including ischemia–reperfusion injury, damage-associated molecular patterns, and immunosuppressive signals—thereby shaping DCs-mediated immune outcomes. From a translational perspective, we discuss emerging DCs-targeted therapeutic strategies, including ex vivo–generated tolDCs therapy, in vivo DCs reprogramming via nanodelivery systems, and cell-free approaches such as extracellular vesicles. Early clinical studies indicate that tolDCs infusion is safe and capable of reshaping host immunity by promoting regulatory T cell expansion while suppressing effector CD8+ T cells and natural killer cells. However, key challenges remain, including phenotypic stability, manufacturing standardization, and potential interactions with conventional immunosuppressive regimens. Finally, we propose that integrating single-cell and spatial transcriptomics with DCs-based biomarkers may enable the identification of“tolerance signatures” for real-time immune monitoring and personalized immunosuppression minimization. Collectively, targeting DCs biology represents a promising strategy to achieve antigen-specific immune tolerance and improve long-term outcomes in liver transplantation.

Communication Author：WANG Wen-Ya , Email:wwya03378@btch.edu.cn