Dendritic Cells in Xenotransplantation : Shaping the Cellular Immune Response Toward Tolerance

Article Article scientifique Revue de la littérature Dendritic Cells in Xenotransplantation : Shaping the Cellular Immune Response Toward Tolerance eng 2025-04-15 2025 author Puga Yung Gisella 0000-0002-2283-7798 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. 666337 author Wakley Tom Laboratory of Translational Immunology, Department of Medicine, University of Geneva, Geneva, Switzerland. 855678 author Kouklas Athanasios 0000-0002-3282-0674 Laboratory of Translational Immunology, Department of Medicine, University of Geneva, Geneva, Switzerland. 973449 author Seebach Jorg Dieter 0000-0001-5748-4577 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. 647894 Département de médecine (DEMED) e70037 10.1111/xen.70037 40243284 0908-665X PMC12005074 https://onlinelibrary.wiley.com/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. DC Dendritic cells Species Tolerance Xenotransplantation Animals Dendritic Cells / immunology Humans Transplantation, Heterologous / methods Graft Rejection / immunology Immune Tolerance / immunology Immunity, Cellular / immunology Swine Heterografts / immunology Transplantation Tolerance / immunology Primates Dewey 616 Swiss National Science Foundation Xeno2Cure - advanced engineering and testing of organ donor pigs 198577 CH Programmes 56 Département de médecine 221 false 518 Cellules NK et récepteurs FcyR dans l'auto-immunité et le rejet de xénotransplantation 856 Xenotransplantation 32 2 4f21cbb7-28dd-4558-ac7a-97e0e27b7af8 Article (Published version) Public Xenotransplantation_-_2025_-_Puga_Y.pdf 1890811 application/pdf CC BY-NC-ND-4.0 ceb9619959fc4b01cf4fed8d00d809d59d9a805d20197cc74f3ba1b7d0bb4566 eb913a2e-0c46-4438-91e4-a608c93d8371 Appendix Public XEN-32-e70037-s001.docx 187568 application/vnd.openxmlformats-officedocument.wordprocessingml.document b42cb7faeafcdaf90eff445d5d01ccd75467f6b7217488f9aeee06ea325d1b2d openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Dendritic Cells in Xenotransplantation : Shaping the Cellular Immune Response Toward Tolerance	Xenotransplantation			2025	56	86

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Wakley, Tom