Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Tolerogenic dendritic cells and their applications in transplantation

Cellular & Molecular Immunology volume 12, pages 24–30 (2015)Cite this article

Abstract

In transplantation immunology, the ultimate goal is always to successfully and specifically induce immune tolerance of allografts. Tolerogenic dendritic cells (tol-DCs) with immunoregulatory functions have attracted much attention as they play important roles in inducing and maintaining immune tolerance. Here, we focused on tol-DCs that have the potential to promote immune tolerance after solid-organ transplantation. We focus on their development and interactions with other regulatory cells, and we also explore various tol-DC engineering protocols. Harnessing tol-DCs represents a promising cellular therapy for promoting long-term graft functional survival in transplant recipients that will most likely be achieved in the future.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Steinman RM . Dendritic cells: understanding immunogenicity. Eur J Immunol 2007; 37( Suppl 1): S53–S60.

    Article  CAS  PubMed  Google Scholar 

  2. Liu J, Han C, Xie B, Wu Y, Liu S, Chen K et al. Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO. Nat Immunol 2014; in press.

  3. Wang P, Xue Y, Han Y, Lin L, Wu C, Xu S et al. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 2014; 344: 310–313.

    Article  CAS  PubMed  Google Scholar 

  4. Shortman K, Naik SH . Steady-state and inflammatory dendritic-cell development. Nat Rev Immunol 2007; 7: 19–30.

    Article  CAS  PubMed  Google Scholar 

  5. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM . Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 2002; 196: 1627–1638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Legge KL, Gregg RK, Maldonado-Lopez R, Li L, Caprio JC, Moser M et al. On the role of dendritic cells in peripheral T cell tolerance and modulation of autoimmunity. J Exp Med 2002; 196: 217–227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cools N, Ponsaerts P, van Tendeloo VF, Berneman ZN . Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 2007; 82: 1365–1374.

    Article  CAS  PubMed  Google Scholar 

  8. Cools N, Petrizzo A, Smits E, Buonaguro FM, Tornesello ML, Berneman Z et al. Dendritic cells in the pathogenesis & treatment of human diseases: a Janus bifrons? Immunotherapy 2011; 3: 1203–1222.

    Article  CAS  PubMed  Google Scholar 

  9. Steinman RM, Banchereau J . Taking dendritic cells into medicine. Nature 2007; 449: 419–426.

    Article  CAS  PubMed  Google Scholar 

  10. Marcelo H, Maria C . Negative vaccination by tolerogenic dendritic cells in organ transplantation. Curr Opin Organ Transplant 2010; 15: 738–743.

    Article  Google Scholar 

  11. Morelli AE, Thomson AW . Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 2007; 7: 610–621.

    Article  CAS  PubMed  Google Scholar 

  12. Pallotta MT, Orabona C, Volpi C, Vacca C, Belladonna ML, Bianchi R et al. Indoleamine 2,3-dioxygenase is a signaling protein in longterm tolerance by dendritic cells. Nat Immunol 2011; 12: 870–878.

    Article  CAS  PubMed  Google Scholar 

  13. Mendieta-Zeron H . Developing immunologic tolerance for transplantation at the fetal stage. Immunotherapy 2011: 3: 1499–1512.

    Article  CAS  PubMed  Google Scholar 

  14. Ezzelarab M, Thomson AW . Tolerogenic dendritic cells and their role in transplantation. Semin Immunol 2011: 23: 252–263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kalantari T, Kamali-Sarvestani E, Ciric B, Karimi MH, Kalantari M, Faridar A et al. Generation of immunogenic and tolerogenic clinical-grade dendritic cells. Immunol Res 2011: 51: 153–160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xia S, Guo Z, Xu X, Yi H, Wang Q, Cao X . Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells, maintaining liver tolerance. Blood 2008; 112: 3175–3185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ilarregui JM, Croci DO, Bianco GA, Toscano MA, Salatino M, Vermeulen ME et al. Tolerogenic signals delivered by dendritic cells to T cells through a galectin-1-driven immunoregulatory circuit involving interleukin 27 and interleukin 10. Nat Immunol 2009; 10: 981–991.

    Article  CAS  PubMed  Google Scholar 

  18. Rémy S, Blancou P, Tesson L, Tardif V, Brion R, Royer PJ et al. Carbon monoxide inhibits TLR-induced dendritic cell immunogenicity. J Immunol 2009; 182: 1877–1884.

    Article  PubMed  CAS  Google Scholar 

  19. Wu L, Liu YJ . Development of dendritic-cell lineages. Immunity 2007; 26: 741–750.

    Article  CAS  PubMed  Google Scholar 

  20. Barratt-Boyes SM, Thomson AW . Dendritic cells: tools and targets for transplant tolerance. Am J Transplant 2005; 5: 2807–2813.

    Article  CAS  PubMed  Google Scholar 

  21. Mukhopadhaya A, Hanafusa T, Jarchum I, Chen YG, Iwai Y, Serreze DV et al. Selective delivery of beta cell antigen to dendritic cells in vivo leads to deletion and tolerance of autoreactive CD8+ T cells in NOD mice. Proc Natl Acad Sci U S A 2008; 105: 6374–6379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Villadangos JA, Heath WR . Life cycle, migration and antigen presenting functions of spleen and lymph node dendritic cells: limitations of the Langerhans cells paradigm. Semin Immunol 2005; 17: 262–272.

    Article  CAS  PubMed  Google Scholar 

  23. Dudziak D, Kamphorst AO, Heidkamp GF, Buchholz VR, Trumpfheller C, Yamazaki S et al. Differential antigen processing by dendritic cell subsets in vivo. Science 2007; 315: 107–111.

    Article  CAS  PubMed  Google Scholar 

  24. Wu WQ, Shan J, Li YP, Luo L, Sun GX, Zhou Y et al. Adoptive transfusion of tolerance dendritic cells prolong the survival of cardiac allograft: a systematic review on 44 animal studies. Chin J Evid-based Med 2012; 5: 139–153.

    Article  Google Scholar 

  25. Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med 2006; 203: 883–895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. McGrath MM, Najafian N . The role of coinhibitory signaling pathways in transplantation and tolerance. Front Immunol 2012; 3: 47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Puliaeva I, Soloviova K, Puliaiev M, Lang T, Puliaev R, Via CS . Enhancement of suboptimal CD8 cytotoxic T cell effector function in vivo using antigen-specific CD80 defective T cells. J Immunol 2011; 186: 291–304.

    Article  CAS  PubMed  Google Scholar 

  28. Yang J, Riella LV, Chock S, Liu T, Zhao X, Yuan X et al. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo. J Immunol 2011; 187: 1113–1119.

    Article  CAS  PubMed  Google Scholar 

  29. Spörri R, Reis e Sousa C . Inflammatory mediators are insufficient for full dendritic cell activation and promote expansion of CD4+ T cell populations lacking helper function. Nat Immunol 2005; 6: 163–170.

    Article  PubMed  CAS  Google Scholar 

  30. Wilson HL, Ni K, O'Neill HC . Identification of progenitor cells in long-term spleen stromal cultures that produce immature dendritic cells. Proc Natl Acad Sci USA 2000; 97: 4784–4789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang M, Tang H, Guo Z, An H, Zhu X, Song W et al. Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol 2004; 5: 1124–1133.

    Article  CAS  PubMed  Google Scholar 

  32. Tang H, Guo Z, Zhang M, Wang J, Chen G, Cao X . Endothelial stroma programs hematopoietic stem cells to differentiate into regulatory dendritic cells through IL-10. Blood 2006; 108: 1189–1197.

    Article  CAS  PubMed  Google Scholar 

  33. Li Q, Guo Z, Xu X, Xia S, Cao X . Pulmonary stromal cells induce the generation of regulatory DC attenuation T-cell-mediated lung inflammation. Eur J Immunol 2008; 38: 2751–2761.

    Article  CAS  PubMed  Google Scholar 

  34. Roozendaal R, Mebius RE . Stromal cell–immune cell interactions. Annu Rev Immunol 2011; 29: 23–43.

    Article  CAS  PubMed  Google Scholar 

  35. Qian C, Cao X . Naturally occurring CD1c+ human regulatory dendritic cells: immunoregulators that are expanded in response to E. coli infection. Eur J Immunol 2012: 42: 1388–1392.

    Article  CAS  PubMed  Google Scholar 

  36. Han Y, Chen Z, Yang Y, Jiang Z, Gu Y, Liu Y et al. Human CD14+ CTLA-4+ regulatory dendritic cells suppress T-cell response by cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase production in hepatocellular carcinoma. Hepatology 2014; 59: 567–579.

    Article  CAS  PubMed  Google Scholar 

  37. Liu Q, Zhang C, Sun A, Zheng Y, Wang L, Cao X . Tumor-educated CD11bhighIalow regulatory dendritic cells suppress T cell response through arginase I. J Immunol 2009; 182: 6207–6216.

    Article  CAS  PubMed  Google Scholar 

  38. Merad M, Sathe P, Helft J, Miller J, Mortha A . The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31: 563–604.

    Article  CAS  PubMed  Google Scholar 

  39. Abe M, Wang Z, de Creus A, Thomson AW . Plasmacytoid dendritic cell precursors induce allogeneic T-cell hyporesponsiveness and prolong heart graft survival. Am J Transplant 2005; 5: 1808–1819.

    Article  CAS  PubMed  Google Scholar 

  40. Lutz MB . Therapeutic potential of semi-mature dendritic cells for tolerance induction. Front Immunol 2012; 3: 123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ochando JC, Homma C, Yang Y, Hidalgo A, Garin A, Tacke F et al. Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat Immunol 2006: 7: 652–662.

    Article  CAS  PubMed  Google Scholar 

  42. Abe M, Colvin BL, Thomson AW . Plasmacytoid dendritic cells: in vivo regulators of alloimmune reactivity? Transplant Proc 2005; 37: 4119–4121.

    Article  CAS  PubMed  Google Scholar 

  43. Arpinati M, Chirumbolo G, Urbini B, Perrone G, Rondelli D, Anasetti C . Role of plasmacytoid dendritic cells in immunity and tolerance after allogeneic hematopoietic stem cell transplantation. Transpl Immunol 2003; 11: 345–356.

    Article  CAS  PubMed  Google Scholar 

  44. Ito T, Yang M, Wang YH, Lande R, Gregorio J, Perng OA et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med 2007; 204: 105–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Colvin BL, Sumpter TL, Tokita D, Salati J, Mellor AL, Thomson AW . Allostimulatory activity of bone marrow-derived plasmacytoid dendritic cells is independent of indoleamine dioxygenase but regulated by inducible costimulator ligand expression. Hum Immunol 2009; 70: 313–320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gilliet M, Liu YJ . Generation of human CD8 T regulatorycells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med 2002; 195: 695–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li XL, Ménoret S, Bezie S, Caron L, Chabannes D, Hill M et al. Mechanism and localization of CD8 regulatory T cells in a heart transplant model of tolerance. J Immunol 2010; 185: 823–833.

    Article  CAS  PubMed  Google Scholar 

  48. Björck P, Coates PT, Wang Z, Duncan FJ, Thomson AW . Promotion of long-term heart allograft survival by combination of mobilized donor plasmacytoid dendritic cells and anti-CD154 monoclonal antibody. J Heart Lung Transplant 2005; 24: 1118–1120.

    Article  PubMed  Google Scholar 

  49. Okazaki T, Honjo T . The PD-1–PD-L pathway in immunological tolerance. Trends Immunol 2006; 27: 195–201.

    Article  CAS  PubMed  Google Scholar 

  50. Tokita D, Mazariegos GV, Zahorchak AF, Chien N, Abe M, Raimondi G et al. High PD-L1/CD86 ratio on plasmacytoid dendritic cells correlates with elevated T-regulatory cells in liver transplant tolerance. Transplantation 2008; 85: 369–377.

    Article  PubMed  Google Scholar 

  51. Chen W, Liang X, Peterson AJ, Munn DH, Blazar BR . The indoleamine 2,3-dioxygenase is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J Immunol 2008; 181: 5396–5404.

    Article  CAS  PubMed  Google Scholar 

  52. Mazariegos GV, Zahorchak AF, Reyes J, Chapman H, Zeevi A, Thomson AW . Dendritic cell subset ratio in tolerant, weaning and nontolerant liver recipients is not affected by extent of immunosuppression. Am J Transplant 2005; 5: 314–322.

    Article  PubMed  Google Scholar 

  53. Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud DJ et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med 2012; 4: 124–128.

    Article  Google Scholar 

  54. Huang Y, Bozulic LD, Miller T, Xu H, Hussain LR, Ildstad ST . CD8α+ plasmacytoid precursor DCs induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo. Blood 2011; 117: 2494–2505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bakdash G, Sittig SP, van Dijk T, Figdor CG, de Vries IJ . The nature of activatory and tolerogenic dendritic cell-derived signal II. Front Immunol 2013; 4: 53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Yamazaki S, Steinman RM . Dendritic cells as controllers of antigen-specific Foxp3+ regulatory T cells. J Dermatol Sci 2009; 54: 69–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hwu P, Du MX, Lapointe R, Do M, Taylor MW, Young HA . Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 2000; 164: 3596–3599.

    Article  CAS  PubMed  Google Scholar 

  58. Belkaid Y, Oldenhove G . Tuning microenvironments: induction of regulatory T cells by dendritic cells. Immunity 2008; 29: 362–371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gomez de Aguero M, Vocanson M, Hacini-Rachinel F, Taillardet M, Sparwasser T, Kissenpfennig A et al. Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8+ T cells and activating Foxp3+ regulatory T cells. J Clin Invest 2012; 122: 1700–1711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Luckey U, Schmidt T, Pfender N, Romer M, Lorenz N, Martin SF et al. Crosstalk of regulatory T cells and tolerogenic dendritic cells prevents contact allergy in subjects with low zone tolerance. J Allergy Clin Immunol 2012; 130: 781–797.

    Article  CAS  PubMed  Google Scholar 

  61. Qian C, Qian L, Yu Y, An H, Guo Z, Han Y et al. Fas signal promotes the immunosuppressive function of regulatory dendritic cells via ERK/β-catenin pathway. J Biol Chem 2013; 288: 27825–27835.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kornete M1, Piccirillo CA . Functional crosstalk between dendritic cells and Foxp3+ regulatory T cells in themaintenance of immune tolerance. Front Immunol 2012; 3: 165.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Gabrysová L, Nicolson KS, Streeter HB, Verhagen J, Sabatos-Peyton CA, Morgan DJ et al. Negative feedback control of the autoimmune response through antigeninduced differentiation of IL-10-secreting Th1 cells. J Exp Med 2009; 206: 1755–1767.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Muth S, Schütze K, Schild H, Probst HC . Release of dendritic cells from cognate CD4+ T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity. Proc Natl Acad Sci USA 2012; 109: 9059–9064.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wu C, Zhang Y, Jiang Y, Wang Q, Long Y, Wang C et al. Apoptotic cell administration enhances pancreatic islet engraftment by induction of regulatory T cells and tolerogenic dendritic cells. Cell Mol Immunol 2013; 10: 393–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Pletinckx K, Dohler A, Pavlovic V, Lutz MB . Role of dendritic cell maturity/costimulation for generation, homeostasis, and suppressive activity of regulatory T cells. Front Immunol 2011; 2: 39.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Volchenkov R, Karlsen M, Jonsson R, Appel S . Type 1 regulatory T cells and regulatory B cells induced by tolerogenic dendritic cells. Scand J Immunol 2013; 77: 246–254.

    Article  CAS  PubMed  Google Scholar 

  68. Giannoukakis N, Trucco M . A role for tolerogenic dendritic cell-induced B-regulatory cells in type 1 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 2012; 19: 279–287.

    Article  CAS  PubMed  Google Scholar 

  69. Lund FE . Cytokine-producing B lymphocytes—key regulators of immunity. Curr Opin Immunol 2008; 20: 332–338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Shaw J, Wang YH, Ito T, Arima K, Liu YJ . Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70. Blood 2010; 115: 3051–3057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Qian L, Qian C, Chen Y, Bai Y, Bao Y, Lu L et al. Regulatory dendritic cells program B cells to differentiate into CD19hiFcγIIbhi regulatory B cells through IFN-β and CD40L. Blood 2012; 120: 581–591.

    Article  CAS  PubMed  Google Scholar 

  72. Sun G, Shan J, Li Y, Zhou Y, Guo Y, Wu W et al. Adoptive infusion of tolerogenic dendritic cells prolongs the survival of pancreatic islet allografts: a systematic review of 13 mouse and rat studies. PLoS ONE 2012; 7: e52096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Fierro A, Mora JR, Bono MR, Morales J, Buckel E, Sauma D et al. Dendritic cells and the mode of action of anticalcineurinic drugs: an integrating hypothesis. Nephrol Dial Transplant 2003; 18: 467–468.

    Article  CAS  PubMed  Google Scholar 

  74. Sauma D, Fierro A, Mora JR, Lennon-Dumenil AM, Bono MR, Rosemblatt M et al. Cyclosporine preconditions dendritic cells during differentiation and reduces IL-2 and IL-12 production following activation: a potential tolerogenic effect. Transplant Proc 2003; 35: 2515–2517.

    Article  CAS  PubMed  Google Scholar 

  75. Nikolic T, Roep BO . Regulatory multitasking of tolerogenic dendritic cells—lessons taken from vitamin D3-treated tolerogenic dendritic cells. Front Immunol 2013; 4: 113.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Hubert P, Jacobs N, Caberg JH, Boniver J, Delvenne P . The cross-talk between dendritic and regulatory T cells: good or evil? J Leukoc Biol 2007; 82: 781–794.

    Article  CAS  PubMed  Google Scholar 

  77. Min WP, Gorczynski R, Huang XY, Kushida M, Kim P, Obataki M et al. Dendritic cells genetically engineered to express Fas ligand induce donorspecific hyporesponsiveness and prolong allograft survival. J Immunol 2000; 164: 161–167.

    Article  CAS  PubMed  Google Scholar 

  78. Fu H, Song S, Liu F, Ni Z, Tang Y, Shen X et al. Dendritic cells transduced with SOCS1 gene exhibit regulatory DC properties and prolong allograft survival. Cell Mol Immunol 2009; 6: 87–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Li M, Zhang X, Zheng X, Lian D, Zhang ZX, Ge W et al. Immune modulation and tolerance induction by RelB-silenced dendritic cells through RNA interference. J Immunol 2007; 178: 5480–5487.

    Article  CAS  PubMed  Google Scholar 

  80. Xu H, Chen T, Wang HQ, Ji MJ, Zhu X, Wu WX . Prolongation of rat intestinal allograft survival by administration of donor interleukin-12 p35-silenced bone marrow-derived dendritic cells. Transplant Proc 2006; 38: 1561–1563.

    Article  CAS  PubMed  Google Scholar 

  81. Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M . Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 2011; 34: 2026–2032.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Kripke ML . Antigenicity of murine skin tumors induced by ultraviolet light. J Natl Cancer Inst 1974; 53: 1333–1336.

    Article  CAS  PubMed  Google Scholar 

  83. Sun E, Gao Y, Chen J, Roberts A, Wang X, Chen Z et al. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient. Cell Death Differ 2004; 11: 1258–1264.

    Article  CAS  PubMed  Google Scholar 

  84. Wang Z, Larregina AT, Shufesky WJ, Perone MJ, Montecalvo A, Zahorchack AF et al. Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T-cell deletion and regulatory T cells. Am J Transplant 2006; 6: 1297–1311.

    Article  CAS  PubMed  Google Scholar 

  85. Zheng DH, Shi BY, Zou YP, Cai M, Qian YY, Shi YC et al. Effect of a novel negative immunoregulatory dendritic cell on Th1/Th2 balance of cardiac allograft recipient rats. Med J Chin PLA 2009; 34: 715–718.

    Google Scholar 

  86. Kumlien G, Genberg H, Shanwell A, Tydén G . Photopheresis for the treatment of refractory renal graft rejection. Transplantation 2005; 79: 123–125.

    Article  PubMed  Google Scholar 

  87. Benden C, Speich R, Hofbauer GF, Irani S, Eich-Wanger C, Russi EW et al. Extracorporeal photopheresis after lung transplantation: a 10-year single-center experience. Transplantation 2008; 86: 1625–1627.

    Article  PubMed  Google Scholar 

  88. Rutella S, Bonanno G, Pierelli L, Mariotti A, Capoluongo E, Contemi AM et al. Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha. Eur J Immunol 2004; 34: 1291–1302.

    Article  CAS  PubMed  Google Scholar 

  89. Lan YY, Wang Z, Raimondi G, Wu W, Colvin BL, de Creus A et al. Alternatively activated dendritic cells preferentially secrete IL-10, expand Foxp3+CD4+ T cells, and induce long-term organ allograft survival in combination with CTLA4-Ig. J Immunol 2006; 177: 5868–5877.

    Article  CAS  PubMed  Google Scholar 

  90. Lutz MB, Suri RM, Niimi M, Ogilvie AL, Kukutsch NA, Rössner S et al. Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol 2000; 30: 1813–1822.

    Article  CAS  PubMed  Google Scholar 

  91. Boks MA, Kager-Groenland JR, Haasjes MS, Zwaginga JJ, van Ham SM, ten Brinke A . IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction a comparative study of human clinical-applicable DC. Clin Immunol 2012; 142: 332–342.

    Article  CAS  PubMed  Google Scholar 

  92. Meredith MM, Liu K, Kamphorst AO, Idoyaga J, Yamane A, Guermonprez P et al. Zinc finger transcription factor zDC is a negative regulator required to prevent activation of classical dendritic cells in the steady state. J Exp Med 2012; 209: 1583–1593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Watkins SK, Hurwitz AA . FOXO3: a master switch for regulating tolerance and immunity in dendritic cells. Oncoimmunology 2012; 1: 252–254.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Kassianos AJ, Hardy MY, Ju X, Vijayan D, Ding Y, Vulink AJ et al. Human CD1c(BDCA-1)+ myeloid dendritic cells secrete IL-10 and display an immunoregulatory phenotype and function in response to Escherichia coli. Eur J Immunol 2012; 42: 1512–1522.

    Article  CAS  PubMed  Google Scholar 

  95. Xiang M, Lu J, Zhang C, Lan Y, Zhou H, Li X et al. Identification and quantification of total coumarins from Urtica dentata Hand and its roles in promoting immune tolerance via TLR4-mediated dendritic cell immaturation. Biosci Biotchnol Biochem 2013; 77: 1200–1206.

    Article  CAS  Google Scholar 

  96. Jung KC, Park CG, Jeon YK, Park HJ, Ban YL, Min HS et al. In situ induction of dendritic cell-based T cell tolerance in humanized mice and nonhuman primates. J Exp Med 2011; 208: 2477–2488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Hackstein H, Thomson AW . Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat Rev Immunol 2004; 4: 24–34.

    Article  CAS  PubMed  Google Scholar 

  98. Fischer RT, Turnquist HR, Wang Z, Beer-Stolz D, Thomson AW . Rapamycin-conditioned, alloantigen-pulsed myeloid dendritic cells present donor MHC class I/peptide via the semi-direct pathway and inhibit survival of antigen-specific CD8+ T cells in vitro and in vivo. Transpl Immunol 2011; 25: 20–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Hu J, Wan Y . Tolerogenic dendritic cells and their potential applications. Immunology 2011; 132: 307–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Liu Q, Chen T, Chen G, Shu X, Sun A, Ma P et al. Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways. Mol Immunol 2007; 44: 2686–2696.

    Article  CAS  PubMed  Google Scholar 

  101. Chen T, Guo J, Yang M, Han C, Zhang M, Chen W et al. Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression. Blood 2004; 103: 413–421.

    Article  CAS  PubMed  Google Scholar 

  102. Ueno H, Schmitt N, Klechevsky E, Pedroza-Gonzalez A, Matsui T, Zurawski G et al. Harnessing human dendritic cell subsets for medicine. Immunol Rev 2010; 234: 199–212.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Watkins SK, Zhu Z, Riboldi E, Shafer-Weaver KA, Stagliano KE, Sklavos MM et al. FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer. J Clin Invest 2011; 121: 1361–1372.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Segura E, Valladeau-Guilemond J, Donnadieu MH, Sastre-Garau X, Soumelis V, Amigorena S . Characterization of resident and migratory dendritic cells in human lymph nodes. J Exp Med 2012; 209: 653–660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Palucka K, Banchereau J, Mellman I . Designing vaccines based on biology of human dendritic cell subsets. Immunity 2010; 33: 464–478.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Belz GT, Behrens GM, Smith CM, Miller JF, Jones C, Lejon K et al. The CD8alpha+ dendritic cell is responsible for inducing peripheral selftolerance to tissue-associated antigens. J Exp Med 2002; 196: 1099–1104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. O'Connell PJ, Son YI, Giermasz A, Wang Z, Logar AJ, Thomson AW et al. Type-1 polarized nature of mouse liver CD8alpha− and CD8alpha+ dendritic cells: tissue-dependent differences offset CD8alpha-related dendritic cell heterogeneity. Eur J Immunol 2003; 33: 2007–2013.

    Article  CAS  PubMed  Google Scholar 

  108. Issa F, Wood KJ . Translating tolerogenic therapies to the clinic—where do we stand? Front Immunol 2012; 3: 254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National High Technology Research and Development Program of China (863 Program; 2012AA021002).

Author information

Authors and Affiliations

  1. The Transplant Institute of the People's Liberation Army, The 309th Hospital, Beijing, China

    Haibin Li & Bingyi Shi

Authors
  1. Haibin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bingyi Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bingyi Shi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, H., Shi, B. Tolerogenic dendritic cells and their applications in transplantation. Cell Mol Immunol 12, 24–30 (2015). https://doi.org/10.1038/cmi.2014.52

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2014.52

Keywords

This article is cited by

Search

Advanced search

Quick links