Tolerogenic dendritic cells in organ transplantation

Dendritic cells (DCs) are specialized cells of the innate immune system that are characterized by their ability to take up, process and present antigens (Ag) to effector T cells. They are derived from DC precursors produced in the bone marrow. Different DC subsets have been described according to lineage‐specific transcription factors required for their development and function. Functionally, DCs are responsible for inducing Ag‐specific immune responses that mediate organ transplant rejection. Consequently, to prevent anti‐donor immune responses, therapeutic strategies have been directed toward the inhibition of DC activation. In addition however, an extensive body of preclinical research, using transplant models in rodents and nonhuman primates, has established a central role of DCs in the negative regulation of alloimmune responses. As a result, DCs have been employed as cell‐based immunotherapy in early phase I/II clinical trials in organ transplantation. Together with in vivo targeting through use of myeloid cell‐specific nanobiologics, DC manipulation represents a promising approach for the induction of transplantation tolerance. In this review, we summarize fundamental characteristics of DCs and their roles in promotion of central and peripheral tolerance. We also discuss their clinical application to promote improved long‐term outcomes in organ transplantation.

• Publication year

  2020

• Venue

  Transplant International

• Publication date

  2020-02-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.1111/tri.13504PMID 31472079PMCID PMC6983332
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Regulatory dendritic cells for human organ transplantation.

  2019cited by this paper
• Extracellular vesicle-mediated MHC cross-dressing in immune homeostasis, transplantation, infectious diseases, and cancer

  2018cited by this paper
• Targeting DEC-205−DCIR2+ dendritic cells promotes immunological tolerance in proteolipid protein-induced experimental autoimmune encephalomyelitis

  2018cited by this paper
• State of the Art: Role of the Dendritic Cell in Induction of Allograft Tolerance.

  2018cited by this paper
• Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival

  2018cited by this paper
• Graft‐infiltrating PD‐L1hi cross‐dressed dendritic cells regulate antidonor T cell responses in mouse liver transplant tolerance

  2018cited by this paper
• Intestinal CD103+CD11b+ cDC2 Conventional Dendritic Cells Are Required for Primary CD4+ T and B Cell Responses to Soluble Flagellin

  2018cited by this paper
• Inhibiting Inflammation with Myeloid Cell‐Specific Nanobiologics Promotes Organ Transplant Acceptance

  2018influential reference
• Nanoparticles for the Induction of Antigen-Specific Immunological Tolerance

  2018cited by this paper
• Tolerogenic Dendritic Cells in Solid Organ Transplantation: Where Do We Stand?

  2018cited by this paper
• Modification of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance

  2017cited by this paper
• Regulatory dendritic cells for promotion of liver transplant operational tolerance: Rationale for a clinical trial and accompanying mechanistic studies.

  2017cited by this paper
• An Antigen-Presenting and Apoptosis-Inducing Polymer Microparticle Prolongs Alloskin Graft Survival by Selectively and Markedly Depleting Alloreactive CD8+ T Cells

  2017cited by this paper
• Tolerance through Education: How Tolerogenic Dendritic Cells Shape Immunity

  2017cited by this paper
• Tolerogenic dendritic cell therapy in organ transplantation

  2017cited by this paper
• High PD-L1/CD86 MFI ratio and IL-10 secretion characterize human regulatory dendritic cells generated for clinical testing in organ transplantation.

  2017cited by this paper
• Nanoparticle-Based Modulation and Monitoring of Antigen-Presenting Cells in Organ Transplantation

  2017influential reference
• Update on Dendritic Cell-Induced Immunological and Clinical Tolerance

  2017cited by this paper
• Prolonged survival effects induced by immature dendritic cells and regulatory T cells in a rat liver transplantation model.

  2016cited by this paper
• Combining Exosomes Derived from Immature DCs with Donor Antigen-Specific Treg Cells Induces Tolerance in a Rat Liver Allograft Model

  2016cited by this paper
• Donor dendritic cell-derived exosomes promote allograft-targeting immune response.

  2016cited by this paper
• Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation

  2016cited by this paper
• Lipoproteins and lipoprotein mimetics for imaging and drug delivery.

  2016cited by this paper
• Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation.

  2016cited by this paper
• Erratum: Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart

  2016cited by this paper
• Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles.

  2016cited by this paper
• Eomesoderminlo CTLA4hi Alloreactive CD8+ Memory T Cells Are Associated With Prolonged Renal Transplant Survival Induced by Regulatory Dendritic Cell Infusion in CTLA4 Immunoglobulin–Treated Nonhuman Primates

  2016cited by this paper
• Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart

  2016cited by this paper
• Restricted dendritic cell and monocyte progenitors in human cord blood and bone marrow

  2015cited by this paper
• DCIR2+ cDC2 DCs and Zbtb32 Restore CD4+ T-Cell Tolerance and Inhibit Diabetes

  2015cited by this paper
• Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow

  2015cited by this paper
• Circulating precursors of human CD1c+ and CD141+ dendritic cells

  2015cited by this paper
• PET Imaging of Tumor-Associated Macrophages with 89Zr-Labeled High-Density Lipoprotein Nanoparticles

  2015cited by this paper
• Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

  2014cited by this paper
• Autologous Dendritic Cells Prolong Allograft Survival Through Tmem176b‐Dependent Antigen Cross‐Presentation

  2014cited by this paper
• Tolerogenic dendritic cells and their applications in transplantation

  2014cited by this paper
• Orchestration of transplantation tolerance by regulatory dendritic cell therapy or in-situ targeting of dendritic cells

  2014cited by this paper
• Dendritic cells, monocytes and macrophages: a unified nomenclature based on ontogeny

  2014cited by this paper
• Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance

  2014influential reference
• Ex-vivo tolerogenic F4/80+ antigen-presenting cells (APC) induce efferent CD8+ regulatory T cell-dependent suppression of experimental autoimmune uveitis

  2014cited by this paper
• A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

  2014cited by this paper
• Cross-Dressing by Donor Dendritic Cells after Allogeneic Bone Marrow Transplantation Contributes to Formation of the Immunological Synapse and Maximizes Responses to Indirectly Presented Antigen

  2014cited by this paper
• The effects of rapamycin on regulatory T cells: its potential time-dependent role in inducing transplant tolerance.

  2014cited by this paper
• Toward immunosuppressive effects on liver transplantation in rat model: tacrolimus loaded poly(ethylene glycol)-poly(D,L-lactide) nanoparticle with longer survival time.

  2014cited by this paper
• Adoptive transfusion of tolerogenic dendritic cells prolongs the survival of liver allograft: a systematic review

  2014cited by this paper
• Regulation of immune responses by extracellular vesicles

  2014cited by this paper
• Development and function of dendritic cell subsets.

  2014cited by this paper
• Imaging macrophages with nanoparticles.

  2014cited by this paper
• Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells

  2013cited by this paper
• Specialized role of migratory dendritic cells in peripheral tolerance induction.

  2013cited by this paper
• Applications of nanotechnology for immunology

  2013cited by this paper
• Cancer in the transplant recipient.

  2013cited by this paper
• Research Highlights and Editors’ Picks

  2013cited by this paper
• Scavenger receptor-BI is a receptor for lipoprotein(a)

  2013cited by this paper
• Dendritic Cells: Master Regulators of the Immune Response

  2013cited by this paper
• Adoptive transfusion of tolerant dendritic cells prolong the survival of renal allografts: a systematic review

  2013cited by this paper
• Regulatory Dendritic Cell Infusion Prolongs Kidney Allograft Survival in Nonhuman Primates

  2013cited by this paper
• Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET

  2012cited by this paper
• Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163.

  2012cited by this paper
• Cross-presentation by dendritic cells

  2012cited by this paper
• Regulatory dendritic cells program B cells to differentiate into CD19hiFcγIIbhi regulatory B cells through IFN-β and CD40L.

  2012cited by this paper
• Tolerance Induction by Exosomes from Immature Dendritic Cells and Rapamycin in a Mouse Cardiac Allograft Model

  2012cited by this paper
• Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis

  2012cited by this paper
• Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10–producing suppressive CD4+ T cells

  2012cited by this paper
• Tolerogenic dendritic cells and negative vaccination in transplantation: from rodents to clinical trials

  2012cited by this paper
• Nanoparticle Delivery of Mycophenolic Acid Upregulates PD‐L1 on Dendritic Cells to Prolong Murine Allograft Survival

  2011cited by this paper
• Ex vivo-expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts.

  2011cited by this paper
• Immunoregulatory properties of heme oxygenase-1.

  2011cited by this paper
• Cell Therapy With Autologous Tolerogenic Dendritic Cells Induces Allograft Tolerance Through Interferon‐Gamma and Epstein‐Barr Virus‐Induced Gene 3

  2011cited by this paper
• Nano-sized drug-loaded micelles deliver payload to lymph node immune cells and prolong allograft survival.

  2011cited by this paper
• In situ induction of dendritic cell–based T cell tolerance in humanized mice and nonhuman primates

  2011cited by this paper
• Tolerogenic dendritic cells and their role in transplantation.

  2011cited by this paper
• Killer artificial antigen-presenting cells deplete alloantigen-specific T cells in a murine model of alloskin transplantation.

  2011cited by this paper
• Exosomes derived from immature bone marrow dendritic cells induce tolerogenicity of intestinal transplantation in rats.

  2011influential reference
• NK Cell Patrolling and Elimination of Donor-Derived Dendritic Cells Favor Indirect Alloreactivity

  2010cited by this paper
• Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation.

  2010cited by this paper
• Dendritic cell-targeted pancreatic beta-cell antigen leads to conversion of self-reactive CD4(+) T cells into regulatory T cells and promotes immunotolerance in NOD mice.

  2010cited by this paper
• Reversal of autoimmunity by boosting memory-like autoregulatory T cells.

  2010cited by this paper
• Nanoparticles and the immune system.

  2010cited by this paper
• Tolerogenic Dendritic Cells Induce CD4+CD25hiFoxp3+ Regulatory T Cell Differentiation from CD4+CD25−/loFoxp3− Effector T Cells

  2010cited by this paper
• Targeting MHC Class I Monomers to Dendritic Cells Inhibits the Indirect Pathway of Allorecognition and the Production of IgG Alloantibodies Leading to Long-Term Allograft Survival

  2010cited by this paper
• Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10

  2009cited by this paper
• In Situ-Targeting of Dendritic Cells with Donor-Derived Apoptotic Cells Restrains Indirect Allorecognition and Ameliorates Allograft Vasculopathy

  2009cited by this paper
• Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity

  2009cited by this paper
• New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles

  2009cited by this paper
• Tolerogenic dendritic cells actively inhibit T cells through heme oxygenase‐1 in rodents and in nonhuman primates

  2009cited by this paper
• Carbon Monoxide Inhibits TLR-Induced Dendritic Cell Immunogenicity1

  2009cited by this paper
• Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis

  2008cited by this paper
• Trogocytosis of MHC-I/Peptide Complexes Derived from Tumors and Infected Cells Enhances Dendritic Cell Cross-Priming and Promotes Adaptive T Cell Responses

  2008cited by this paper
• Prolongation of Composite Tissue Allograft Survival by Immature Recipient Dendritic Cells Pulsed with Donor Antigen and Transient Low-Dose Immunosuppression

  2008cited by this paper
• Delivery of rapamycin by PLGA nanoparticles enhances its suppressive activity on dendritic cells.

  2008cited by this paper
• Delivery of rapamycin-loaded nanoparticle down regulates ICAM-1 expression and maintains an immunosuppressive profile in human CD34+ progenitor-derived dendritic cells.

  2008cited by this paper
• CD8+CD205+ Splenic Dendritic Cells Are Specialized to Induce Foxp3+ Regulatory T Cells1

  2008cited by this paper
• Long-Term Survival of Limb Allografts Induced by Pharmacologically Conditioned, Donor Alloantigen-Pulsed Dendritic Cells Without Maintenance Immunosuppression

  2008cited by this paper
• Tolerogenic dendritic cells and the quest for transplant tolerance

  2007cited by this paper
• Rapamycin-Conditioned Dendritic Cells Are Poor Stimulators of Allogeneic CD4+ T Cells, but Enrich for Antigen-Specific Foxp3+ T Regulatory Cells and Promote Organ Transplant Tolerance1

  2007cited by this paper
• Differential Antigen Processing by Dendritic Cell Subsets in Vivo

  2007cited by this paper
• Immune Modulation and Tolerance Induction by RelB-Silenced Dendritic Cells through RNA Interference1

  2007cited by this paper
• Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming.

  2006cited by this paper
• Dendritic Cells Activated by Lipopolysaccharide after Dexamethasone Treatment Induce Donor-Specific Allograft Hyporesponsiveness

  2006cited by this paper

• Innovative approaches targeting innate immune cells to promote organ transplant tolerance.

  2026cites this paper
• Immunology in corneal transplantation-From homeostasis to graft rejection.

  2025cites this paper
• Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation.

  2025cites this paper
• Dendritic Cells in Xenotransplantation: Shaping the Cellular Immune Response Toward Tolerance

  2025cites this paper
• Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 2: implementation strategies

  2025cites this paper
• Rapamycin-modified CD169low/-tolDC promotes skin graft survival in mice via IL-10+Breg.

  2025cites this paper
• Harnessing monocyte-derived dendritic cells for evaluating T cell response by mixed leukocyte reaction

  2025cites this paper
• Potential Biomarkers of Therapeutic Response to ECP in Solid Organ Transplantation

  2025cites this paper
• Induction of Tolerogenic Dendritic Cells by a Noncoding Oligonucleotide

  2025cites this paper
• Use of regulatory cells for achieving functional tolerance of pig heart xenotransplants in humans: a literature review

  2025cites this paper
• Hydrogels in the Immune Context: In Vivo Applications for Modulating Immune Responses in Cancer Therapy

  2025cites this paper
• Injectable Genetic Engineering Hydrogel for Promoting Spatial Tolerance of Transplanted Kidney in Situ

  2024cites this paper
• The Potential of Anti-Inflammatory DC Immunotherapy in Improving Proteinuria in Type 2 Diabetes Mellitus

  2024cites this paper
• The Human Neonatal Skin Fibroblast, an Available Cell Source for Tissue Production and Transplantation, Exhibits Low Risk of Immunogenicity In Vitro

  2024cites this paper
• Unlocking Transplant Tolerance with Biomaterials

  2024cites this paper
• Negative Vaccination Strategies for Promotion of Transplant Tolerance

  2024cites this paper
• High-throughput screening identification of novel immunomodulatory combinations for the generation of tolerogenic dendritic cells

  2024cites this paper
• Epigenetic signature of human vitamin D3 and IL-10 conditioned regulatory DCs

  2024cites this paper
• Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosis

  2024cites this paper
• Tolerogenic dendritic cells and TLR4/IRAK4/NF-κB signaling pathway in allergic rhinitis

  2023cites this paper
• Exopolysaccharide-treated Dendritic Cells Effectively Ameliorate Acute Graft vs Host Disease.

  2023cites this paper
• Innate immune cellular therapeutics in transplantation

  2023cites this paper
• miR-27a-3p alleviates lung transplantation-induced bronchiolitis obliterans syndrome (BOS) via suppressing Smad-mediated myofibroblast differentiation and TLR4-induced dendritic cells maturation.

  2023cites this paper
• Regulatory dendritic cell therapy in organ transplantation

  2023cites this paper
• Manufacturing and validation of Good Manufacturing Practice-compliant regulatory dendritic cells for infusion into organ transplant recipients.

  2023cites this paper
• Donor-derived regulatory dendritic cell infusion modulates effector CD8+ T cell and NK cell responses after liver transplantation

  2023cites this paper
• Tolerogenic dendritic cells in type 1 diabetes: no longer a concept

  2023cites this paper
• Dendritic cells in liver transplantation immune response

  2023cites this paper
• The Immunological Effect of Oxygen Carriers on Normothermic Ex Vivo Liver Perfusion

  2022cites this paper
• Emerging immunomodulatory strategies for cell therapeutics.

  2022cites this paper
• Tolerogenic Dendritic Cells Induce Apoptosis-Independent T Cell Hyporesponsiveness of SARS-CoV-2-Specific T Cells in an Antigen-Specific Manner

  2022cites this paper
• Why Machines will Never Rule the World; Artificial Intelligence without Fear

  2022cites this paper
• Immunotolerance in liver transplantation: a primer for the clinician.

  2022cites this paper
• Current state of clinical trials regarding liver transplant rejection.

  2021cites this paper
• Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival

  2021cites this paper
• Regulatory T Cells for the Induction of Transplantation Tolerance.

  2021cites this paper
• Regulatory Cell Therapy in Organ Transplantation: Achievements and Open Questions

  2021cites this paper
• Myeloid and Mesenchymal Stem Cell Therapies for Solid Organ Transplant Tolerance

  2021cites this paper
• Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages

  2021cites this paper
• Inflammatory processes in the liver: divergent roles in homeostasis and pathology

  2021cites this paper
• Progress toward the Clinical Application of Mesenchymal Stromal Cells and Other Disease-Modulating Regenerative Therapies: Examples from the Field of Nephrology.

  2021cites this paper
• Dendritic Cells: Versatile Players in Renal Transplantation

  2021influential citation
• Dynamics of circulating dendritic cells and cytokines after kidney transplantation—No effect of remote ischaemic conditioning

  2021cites this paper
• Local delivery strategies to restore immune homeostasis in the context of inflammation.

  2021cites this paper
• Cyclosporine A, in Contrast to Rapamycin, Affects the Ability of Dendritic Cells to Induce Immune Tolerance Mechanisms

  2021cites this paper
• Adoptive transfer of GRP78‐treated dendritic cells alleviates insulitis in NOD mice

  2021cites this paper
• Transcriptomic Analysis Identifies A Tolerogenic Dendritic Cell Signature

  2021cites this paper
• Towards regulatory cellular therapies in solid organ transplantation.

  2021cites this paper
• CXCR4 blockade reduces the severity of murine heart allograft rejection by plasmacytoid dendritic cell-mediated immune regulation

  2021cites this paper
• Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

  2020cites this paper
• Special Review: The future of Immunotherapy

  2020cites this paper
• Tolerogenic Dendritic Cells in Autoimmunity and Inflammatory Diseases.

  2020cites this paper
• Suppression of liver transplant rejection by anti-donor MHC antibodies via depletion of donor immunogenic dendritic cells

  2020cites this paper
• Cellular therapies in organ transplantation

  2020cites this paper
• Decoding the Heterogeneity of Human Dendritic Cell Subsets.

  2020cites this paper
• Donor‐derived regulatory dendritic cell infusion results in host cell cross‐dressing and T cell subset changes in prospective living donor liver transplant recipients

  2020cites this paper
• Manipulation of Regulatory Dendritic Cells for Induction Transplantation Tolerance

  2020cites this paper
• Galangin treatment during dendritic cell differentiation confers tolerogenic properties in response to lipopolysaccharide stimulation.

  2020cites this paper
• Mir‐27a‐3p attenuates bronchiolitis obliterans in vivo via the regulation of dendritic cells’ maturation and the suppression of myofibroblasts’ differentiation

  2020cites this paper
• Corneal xenotransplantation: Where are we standing?

  2020cites this paper
• Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer

  2020cites this paper
• Progress in Liver Transplant Tolerance and Tolerance-Inducing Cellular Therapies

  2020influential citation
• Targeting Dendritic Cells with Antigen-Delivering Antibodies for Amelioration of Autoimmunity in Animal Models of Multiple Sclerosis and Other Autoimmune Diseases

  2020cites this paper
• The Role of Diverse Liver Cells in Liver Transplantation Tolerance

  2020cites this paper
• Dendritic cells with METTL3 gene knockdown exhibit immature properties and prolong allograft survival

  2020cites this paper
• Tolerizing Strategies for the Treatment of Autoimmune Diseases: From ex vivo to in vivo Strategies

  2020cites this paper
• Kidney dendritic cells: fundamental biology and functional roles in health and disease

  2020cites this paper
• Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival

  2020cites this paper
• Generation and functional assessment of nonhuman primate regulatory dendritic cells and their therapeutic efficacy in renal transplantation.

  2020cites this paper