Puga Yung Gisella L, Wakley Tom, Kouklas Athanasios, Seebach Jörg D
Division of Immunology and Allergology, Department of Medicine, University Hospitals Geneva, Geneva, Switzerland.
Laboratory of Translational Immunology, Department of Medicine, University of Geneva, Geneva, Switzerland.
Xenotransplantation. 2025 Mar-Apr;32(2):e70037. doi: 10.1111/xen.70037.
The molecular barriers that cause acute xenograft rejection have been identified and addressed by generating genetically modified (GM) animals, knocked out for specific xenoantigens (xenoAgs), and expressing regulatory molecules for both complement and coagulation pathways among others. The focus of xenotransplantation research now lies in delayed xenograft rejection. Dendritic cells (DC) are a specific subpopulation of professional antigen-presenting cells (APC) that play a crucial role in the context of organ transplantation. DCs, originating from both the xenograft and the recipient, have the capacity to present xenoAgs to the recipient's immune system via their respective major histocompatibility complex (MHC) molecules leading to rejection. These processes are known as direct and indirect presentation, respectively. However, under certain microenvironmental conditions, DC develops into anti-inflammatory regulatory cells that can induce immunological tolerance. The purpose of this review is to summarize current knowledge on the general characteristics and functions of DC from species relevant to xenotransplantation, specifically humans, non-human primates (NHP), and pigs. It will also cover the process of xenoAg presentation, different methods for generating DC with regulatory properties in vitro, and finally, discuss the current strategies for using regulatory DC to improve xenograft acceptance by inducing tolerance.
通过培育基因改造（GM）动物，使其特定异种抗原（xenoAgs）缺失，并表达补体和凝血途径等的调控分子，导致急性异种移植排斥反应的分子屏障已被识别并得到解决。异种移植研究的重点现在在于延迟性异种移植排斥反应。树突状细胞（DC）是专职抗原呈递细胞（APC）的一个特定亚群，在器官移植背景下发挥关键作用。源自异种移植物和受体的DC能够通过各自的主要组织相容性复合体（MHC）分子将xenoAgs呈递给受体的免疫系统，从而导致排斥反应。这些过程分别被称为直接呈递和间接呈递。然而，在某些微环境条件下，DC会发育成抗炎调节细胞，能够诱导免疫耐受。本综述的目的是总结关于与异种移植相关物种（特别是人类、非人类灵长类动物（NHP）和猪）的DC的一般特征和功能的现有知识。它还将涵盖xenoAg呈递过程、体外产生具有调节特性的DC的不同方法，最后讨论目前使用调节性DC通过诱导耐受来提高异种移植接受度的策略。
