Table of Contents Author Guidelines Submit a Manuscript
Mediators of Inflammation
Volume 2015, Article ID 513295, 20 pages
http://dx.doi.org/10.1155/2015/513295
Review Article

Role of the Immunogenic and Tolerogenic Subsets of Dendritic Cells in Multiple Sclerosis

1Neuroscience Center, Department of Neurology, The First Hospital of Jilin University, Changchun 130021, China
2Department of Neurobiology, Care Sciences and Society, Karolinska Institute, 141 86 Stockholm, Sweden

Received 24 August 2014; Revised 1 January 2015; Accepted 1 January 2015

Academic Editor: Fumio Tsuji

Copyright © 2015 Zhong-Xiang Xie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. W. Peterson, L. Bö, S. Mörk, A. Chang, and B. D. Trapp, “Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions,” Annals of Neurology, vol. 50, no. 3, pp. 389–400, 2001. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Merad, P. Sathe, J. Helft, J. Miller, and A. Mortha, “The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting,” Annual Review of Immunology, vol. 31, pp. 563–604, 2013. View at Publisher · View at Google Scholar · View at Scopus
  3. D. Vremec, J. Pooley, H. Hochrein, L. Wu, and K. Shortman, “CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen,” Journal of Immunology, vol. 164, no. 6, pp. 2978–2986, 2000. View at Publisher · View at Google Scholar · View at Scopus
  4. K. Shortman and Y. J. Liu, “Mouse and human dendritic cell subtypes,” Nature Reviews Immunology, vol. 2, no. 3, pp. 151–161, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. R. Maldonado-Lopez, T. de Smedt, P. Michelet et al., “CD8alpha+ and CD8alpha− subclasses of dendritic cells direct the development of distinct T helper cells in vivo,” The Journal of Experimental Medicine, vol. 189, no. 3, pp. 587–592, 1999. View at Google Scholar
  6. B. Pulendran, J. L. Smith, G. Caspary et al., “Distinct dendritic cell subsets differentially regulate the class of immune response in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 3, pp. 1036–1041, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Piccioli, S. Tavarini, E. Borgogni et al., “Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets,” Blood, vol. 109, no. 12, pp. 5371–5379, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. L. Ziegler-Heitbrock, “The CD14+ CD16+ blood monocytes: their role in infection and inflammation,” Journal of Leukocyte Biology, vol. 81, no. 3, pp. 584–592, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. D. Mittag, A. I. Proietto, T. Loudovaris et al., “Human dendritic cell subsets from spleen and blood are similar in phenotype and function but modified by donor health status,” Journal of Immunology, vol. 186, no. 11, pp. 6207–6217, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. S. L. Jongbloed, A. J. Kassianos, K. J. McDonald et al., “Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens,” Journal of Experimental Medicine, vol. 207, no. 6, pp. 1247–1260, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. G. Schreibelt, J. Tel, K. H. E. W. J. Sliepen et al., “Toll-like receptor expression and function in human dendritic cell subsets: implications for dendritic cell-based anti-cancer immunotherapy,” Cancer Immunology, Immunotherapy, vol. 59, no. 10, pp. 1573–1582, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. A. J. Kassianos, M. Y. Hardy, X. Ju et al., “Human CD1c (BDCA-1)+ myeloid dendritic cells secrete IL-10 and display an immuno-regulatory phenotype and function in response to Escherichia coli,” European Journal of Immunology, vol. 42, no. 6, pp. 1512–1522, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. A. Dzionek, A. Fuchs, P. Schmidt et al., “BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood,” The Journal of Immunology, vol. 165, no. 11, pp. 6037–6046, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. F. P. Siegal, N. Kadowaki, M. Shodell et al., “The nature of the principal type 1 interferon-producing cells in human blood,” Science, vol. 284, no. 5421, pp. 1835–1837, 1999. View at Publisher · View at Google Scholar · View at Scopus
  15. N. Kadowaki, S. Antonenko, J. Y.-N. Lau, and Y.-J. Liu, “Natural interferon α/β-producing cells link innate and adaptive immunity,” The Journal of Experimental Medicine, vol. 192, no. 2, pp. 219–225, 2000. View at Publisher · View at Google Scholar · View at Scopus
  16. G. Jego, A. K. Palucka, J. P. Blanck, C. Chalouni, V. Pascual, and J. Banchereau, “Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6,” Immunity, vol. 19, no. 2, pp. 225–234, 2003. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Schwab, A. L. Zozulya, B. C. Kieseier, K. V. Toyka, and H. Wiendl, “An imbalance of two functionally and phenotypically different subsets of plasmacytoid dendritic cells characterizes the dysfunctional immune regulation in multiple sclerosis,” The Journal of Immunology, vol. 184, no. 9, pp. 5368–5374, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Mittelbrunn, G. M. Del Hoyo, L.-B. María et al., “Imaging of plasmacytoid dendritic cell interactions with T cells,” Blood, vol. 113, no. 1, pp. 75–84, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. H. Ueno, N. Schmitt, E. Klechevsky et al., “Harnessing human dendritic cell subsets for medicine,” Immunological Reviews, vol. 234, no. 1, pp. 199–212, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. W. Chen, X. Liang, A. J. Peterson, D. H. Munn, and B. R. Blazar, “The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation,” The Journal of Immunology, vol. 181, no. 8, pp. 5396–5404, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Ito, M. Yang, Y.-H. Wang et al., “Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand,” The Journal of Experimental Medicine, vol. 204, no. 1, pp. 105–115, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Isaksson, B. A. Lundgren, K. M. Ahlgren, O. Kämpe, and A. Lobell, “Conditional DC depletion does not affect priming of encephalitogenic Th cells in EAE,” European Journal of Immunology, vol. 42, no. 10, pp. 2555–2563, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. M. B. Lutz, “Therapeutic potential of semi-mature dendritic cells for tolerance induction,” Frontiers in Immunology, vol. 3, article 123, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Locafaro, G. Amodio, D. Tomasoni, C. Tresoldi, F. Ciceri, and S. Gregori, “HLA-G expression on blasts and tolerogenic cells in patients affected by acute myeloid leukemia,” Journal of Immunology Research, vol. 2014, no. 10, Article ID 636292, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. A. E. Morelli and A. W. Thomson, “Tolerogenic dendritic cells and the quest for transplant tolerance,” Nature Reviews Immunology, vol. 7, no. 8, pp. 610–621, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. C. A. Colton, “Immune heterogeneity in neuroinflammation: dendritic cells in the brain,” Journal of Neuroimmune Pharmacology, vol. 8, no. 1, pp. 145–162, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. G. Brandacher, R. Margreiter, and D. Fuchs, “Clinical relevance of indoleamine 2,3-dioxygenase for alloimmunity and transplantation,” Current Opinion in Organ Transplantation, vol. 13, no. 1, pp. 10–15, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. R. A. Maldonado and U. H. von Andrian, “How tolerogenic dendritic cells induce regulatory T cells,” Advances in Immunology, vol. 108, pp. 111–165, 2010. View at Publisher · View at Google Scholar
  29. H. Jonuleit, E. Schmitt, G. Schuler, J. Knop, and A. H. Enk, “Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells,” The Journal of Experimental Medicine, vol. 192, no. 9, pp. 1213–1222, 2000. View at Publisher · View at Google Scholar · View at Scopus
  30. C. M. U. Hilkens, J. D. Isaacs, and A. W. Thomson, “Development of dendritic cell-based immunotherapy for autoimmunity,” International Reviews of Immunology, vol. 29, no. 2, pp. 156–183, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. P. G. McMenamin, “Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations,” Journal of Comparative Neurology, vol. 405, no. 4, pp. 553–562, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. J.-M. Serot, M. C. Béné, B. Foliguet, and G. C. Faure, “Monocyte-derived IL-10-secreting dendritic cells in choroid plexus epithelium,” Journal of Neuroimmunology, vol. 105, no. 2, pp. 115–119, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Pashenkov, Y.-M. Huang, V. Kostulas, M. Haglund, M. Söderström, and H. Link, “Two subsets of dendritic cells are present in human cerebrospinal fluid,” Brain, vol. 124, no. 3, pp. 480–492, 2001. View at Publisher · View at Google Scholar · View at Scopus
  34. C. Prodinger, J. Bunse, M. Krüger et al., “CD11c-expressing cells reside in the juxtavascular parenchyma and extend processes into the glia limitans of the mouse nervous system,” Acta Neuropathologica, vol. 121, no. 4, pp. 445–458, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. L. Santambrogio, S. L. Belyanskaya, F. R. Fischer et al., “Developmental plasticity of CNS microglia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 11, pp. 6295–6300, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. H.-G. Fischer and G. Reichmann, “Brain dendritic cells and macrophages/microglia in central nervous system inflammation,” The Journal of Immunology, vol. 166, no. 4, pp. 2717–2726, 2001. View at Publisher · View at Google Scholar · View at Scopus
  37. D. O. Willenborg and M. A. Staykova, “Cytokines in the pathogenesis and therapy of autoimmune encephalomyelitis and multiple sclerosis,” Advances in Experimental Medicine and Biology, vol. 520, pp. 96–119, 2003. View at Google Scholar · View at Scopus
  38. L. van de Laar, P. J. Coffer, and A. M. Woltman, “Regulation of dendritic cell development by GM-CSF: molecular control and implications for immune homeostasis and therapy,” Blood, vol. 119, no. 15, pp. 3383–3393, 2012. View at Publisher · View at Google Scholar · View at Scopus
  39. J. F. Curtin, G. D. King, C. Barcia et al., “Fins-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain,” Journal of Immunology, vol. 176, no. 6, pp. 3566–3577, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. N. Anandasabapathy, G. D. Victora, M. Meredith et al., “Flt3L controls the development of radiosensitive dendritic cells in the meninges and choroid plexus of the steady-state mouse brain,” The Journal of Experimental Medicine, vol. 208, no. 8, pp. 1695–1705, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. X. Zhang and S. Markovic-Plese, “Interferon beta inhibits the Th17 cell-mediated autoimmune response in patients with relapsing-remitting multiple sclerosis,” Clinical Neurology and Neurosurgery, vol. 112, no. 7, pp. 641–645, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. I. Tsunoda and R. S. Fujinami, “Inside-out versus outside-in models for virus induced demyelination: axonal damage triggering demyelination,” Springer Seminars in Immunopathology, vol. 24, no. 2, pp. 105–125, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. F. Sato, H. Tanaka, F. Hasanovic, and I. Tsunoda, “Theiler's virus infection: pathophysiology of demyelination and neurodegeneration,” Pathophysiology, vol. 18, no. 1, pp. 31–41, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. R. Huizinga, N. Heijmans, P. Schubert et al., “Immunization with neurofilament light protein induces spastic paresis and axonal degeneration in biozzi ABH mice,” Journal of Neuropathology & Experimental Neurology, vol. 66, no. 4, pp. 295–304, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. P. K. Stys, G. W. Zamponi, J. van Minnen, and J. J. G. Geurts, “Will the real multiple sclerosis please stand up?” Nature Reviews Neuroscience, vol. 13, no. 7, pp. 507–514, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. D. Ganguly, S. Haak, V. Sisirak, and B. Reizis, “The role of dendritic cells in autoimmunity,” Nature Reviews Immunology, vol. 13, no. 8, pp. 566–577, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. S. S. Diebold, “Determination of T-cell fate by dendritic cells,” Immunology and Cell Biology, vol. 86, no. 5, pp. 389–397, 2008. View at Publisher · View at Google Scholar · View at Scopus
  48. E. M. Frohman, M. K. Racke, and C. S. Raine, “Medical progress: multiple sclerosis—the plaque and its pathogenesis,” The New England Journal of Medicine, vol. 354, no. 9, pp. 942–955, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Slavin, L. Kelly-Modis, M. Labadia, K. Ryan, and M. L. Brown, “Pathogenic mechanisms and experimental models of multiple sclerosis,” Autoimmunity, vol. 43, no. 7, pp. 504–513, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Greter, F. L. Heppner, M. P. Lemos et al., “Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis,” Nature Medicine, vol. 11, no. 3, pp. 328–334, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. E. J. McMahon, S. L. Bailey, C. V. Castenada, H. Waldner, and S. D. Miller, “Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis,” Nature Medicine, vol. 11, no. 3, pp. 335–339, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. M. J. McGeachy, L. A. Stephens, and S. M. Anderton, “Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system,” The Journal of Immunology, vol. 175, no. 5, pp. 3025–3032, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Hirata, H. Matsuyoshi, D. Fukuma et al., “Involvement of regulatory T cells in the experimental autoimmune encephalomyelitis-preventive effect of dendritic cells expressing myelin oligodendrocyte glycoprotein plus TRAIL,” Journal of Immunology, vol. 178, no. 2, pp. 918–925, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. N. Yogev, F. Frommer, D. Lukas et al., “Dendritic cells ameliorate autoimmunity in the cns by controlling the homeostasis of PD-1 receptor+ regulatory T cells,” Immunity, vol. 37, no. 2, pp. 264–275, 2012. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Takizawa, T. Kaneyama, S. Tsuganeet et al., “Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease,” Journal of Neuroimmunology, vol. 274, no. 1-2, pp. 78–85, 2014. View at Publisher · View at Google Scholar
  56. S. L. Bailey-Bucktrout, S. C. Caulkins, G. Goings, J. A. A. Fischer, A. Dzionek, and S. D. Miller, “Cutting edge: central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis,” The Journal of Immunology, vol. 180, no. 10, pp. 6457–6461, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Irla, N. Küpfer, T. Suter et al., “MHC class II-restricted antigen presentation by plasmacytoid dendritic cells inhibits T cell-mediated autoimmunity,” Journal of Experimental Medicine, vol. 207, no. 9, pp. 1891–1905, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. Y.-M. Huang, B.-G. Xiao, V. Özenci et al., “Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines,” Journal of Neuroimmunology, vol. 99, no. 1, pp. 82–90, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Pashenkov, N. Teleshova, M. Kouwenhoven et al., “Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple sclerosis and acute optic neuritis,” Clinical & Experimental Immunology, vol. 127, no. 3, pp. 519–526, 2002. View at Publisher · View at Google Scholar · View at Scopus
  60. G. F. Wu and T. M. Laufer, “The role of dendritic cells in multiple sclerosis,” Current Neurology and Neuroscience Reports, vol. 7, no. 3, pp. 245–252, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Karni, M. Abraham, A. Monsonego et al., “Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response,” Journal of Immunology, vol. 177, no. 6, pp. 4196–4202, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. C. López, M. Comabella, H. Al-zayat, M. Tintoré, and X. Montalban, “Altered maturation of circulating dendritic cells in primary progressive MS patients,” Journal of Neuroimmunology, vol. 175, no. 1-2, pp. 183–191, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. A. Vaknin-Dembinsky, G. Murugaiyan, D. A. Hafler, A. L. Astier, and H. L. Weiner, “Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis,” Journal of Neuroimmunology, vol. 195, no. 1-2, pp. 140–145, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. L. A. Boven, L. Montagne, H. S. L. M. Nottet, and C. J. A. de Groot, “Macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and RANTES mRNA semiquantification and protein expression in active demyelinating multiple sclerosis (MS) lesions,” Clinical and Experimental Immunology, vol. 122, no. 2, pp. 257–263, 2000. View at Publisher · View at Google Scholar · View at Scopus
  65. R. Lande, V. Gafa, B. Serafini et al., “Plasmacytoid dendritic cells in multiple sclerosis: intracerebral recruitment and impaired maturation in response to interferon-β,” Journal of Neuropathology and Experimental Neurology, vol. 67, no. 5, pp. 388–401, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. A. L. F. Longhini, F. von Glehn, C. O. Brandão et al., “Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse,” Journal of Neuroinflammation, vol. 8, no. 1, article 2, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Stasiolek, A. Bayas, N. Kruse et al., “Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis,” Brain, vol. 129, no. 5, pp. 1293–1305, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. L. L. Aung, P. Fitzgerald-Bocarsly, S. Dhib-Jalbut, and K. Balashov, “Plasmacytoid dendritic cells in multiple sclerosis: chemokine and chemokine receptor modulation by interferon-beta,” Journal of Neuroimmunology, vol. 226, no. 1-2, pp. 158–164, 2010. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Navarro, C. Aristimuño, S. Sánchez-Ramón et al., “Circulating dendritic cells subsets and regulatory T-cells at multiple sclerosis relapse: differential short-term changes on corticosteroids therapy,” Journal of Neuroimmunology, vol. 176, no. 1-2, pp. 153–161, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. M.-S. Krystyna, T. Jacek, R. Sebastian et al., “Changes in circulating dendritic cells and B-cells in patients with multiple sclerosis relapse during corticosteroid therapy,” Journal of Neuroimmunology, vol. 207, no. 1-2, pp. 107–110, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. Y.-M. Huang, N. Stoyanova, Y.-P. Jin et al., “Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-β and IL-10,” Clinical and Experimental Immunology, vol. 124, no. 2, pp. 306–314, 2001. View at Publisher · View at Google Scholar · View at Scopus
  72. H. C. Heystek, B. den Drijver, M. L. Kapsenberg, R. A. W. van Lier, and E. C. de Jong, “Type I IFNs differentially modulate IL-12p70 production by human dendritic cells depending on the maturation status of the cells and counteract IFN-γ-mediated signaling,” Clinical Immunology, vol. 107, no. 3, pp. 170–177, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. X. Zhang, J. Jin, Y. Tang, D. Speer, D. Sujkowska, and S. Markovic-Plese, “IFN-β1a inhibits the secretion of Th17-polarizing cytokines in human dendritic cells via TLR7 up-regulation,” Journal of Immunology, vol. 182, no. 6, pp. 3928–3936, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. C. M. Sweeney, R. Lonergan, S. A. Basdeo et al., “IL-27 mediates the response to IFN-β therapy in multiple sclerosis patients by inhibiting Th17 cells,” Brain, Behavior, and Immunity, vol. 25, no. 6, pp. 1170–1181, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. E. Wiesemann, D. Sönmez, F. Heidenreich, and A. Windhagen, “Interferon-β increases the stimulatory capacity of monocyte-derived dendritic cells to induce IL-13, IL-5 and IL-10 in autologous T-cells,” Journal of Neuroimmunology, vol. 123, no. 1-2, pp. 160–169, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. B. Schreiner, M. Mitsdoerffer, B. C. Kieseier et al., “Interferon-β enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis,” Journal of Neuroimmunology, vol. 155, no. 1-2, pp. 172–182, 2004. View at Publisher · View at Google Scholar · View at Scopus
  77. D. S. Kim, K. S. Cho, Y. H. Lee, N. H. Cho, Y. T. Oh, and S. J. Hong, “High-grade hydronephrosis predicts poor outcomes after radical cystectomy in patients with bladder cancer,” Journal of Korean Medical Science, vol. 25, no. 3, pp. 369–373, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Chen, G. Chen, S. Deng, X. Liu, G. J. Hutton, and J. Hong, “IFN-β induces the proliferation of CD4+CD25+Foxp3+ regulatory T cells through upregulation of GITRL on dendritic cells in the treatment of multiple sclerosis,” Journal of Neuroimmunology, vol. 242, no. 1-2, pp. 39–46, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. L. L. Aung, A. Brooks, S. A. Greenberg, M. L. Rosenberg, S. Dhib-Jalbut, and K. E. Balashov, “Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells,” Journal of Neuroimmunology, vol. 250, no. 1-2, pp. 99–105, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Bakshi, V. Chalifa-Caspi, I. Plaschkes, I. Perevozkin, M. Gurevich, and R. Schwartz, “Gene expression analysis reveals functional pathways of glatiramer acetate activation,” Expert Opinion on Therapeutic Targets, vol. 17, no. 4, pp. 351–362, 2013. View at Publisher · View at Google Scholar · View at Scopus
  81. Y. Hussien, A. Sanna, M. Söderström, H. Link, and Y.-M. Huang, “Glatiramer acetate and IFN-beta act on dendritic cells in multiple sclerosis,” Journal of Neuroimmunology, vol. 121, no. 1-2, pp. 102–110, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. P. L. Vieira, H. C. Heystek, J. Wormmeester, E. A. Wierenga, and M. L. Kapsenberg, “Glatiramer acetate (copolymer-1, copaxone) promotes Th2 cell development and increased IL-10 production through modulation of dendritic cells,” Journal of Immunology, vol. 170, no. 9, pp. 4483–4488, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Begum-Haque, M. Christy, Y. Wang et al., “Glatiramer acetate biases dendritic cells towards an anti-inflammatory phenotype by modulating OPN, IL-17, and RORγt responses and by increasing IL-10 production in experimental allergic encephalomyelitis,” Journal of Neuroimmunology, vol. 254, no. 1-2, pp. 117–124, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Ruggieri, C. Pica, A. Lia et al., “Combination treatment of Glatiramer Acetate and Minocycline affects phenotype expression of blood monocyte-derived dendritic cells in Multiple Sclerosis patients,” Journal of Neuroimmunology, vol. 197, no. 2, pp. 140–146, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. F. Sellebjerg, D. Hesse, S. Limborg et al., “Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis,” Multiple Sclerosis, vol. 19, no. 2, pp. 179–187, 2013. View at Publisher · View at Google Scholar · View at Scopus
  86. K. L. Sand, E. Knudsen, J. Rolin, Y. Al-Falahi, and A. A. Maghazachi, “Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate,” Cellular and Molecular Life Sciences, vol. 66, no. 8, pp. 1446–1456, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. M. del Pilar Martin, P. D. Cravens, R. Winger et al., “Decrease in the numbers of dendritic cells and CD4+ T cells in cerebral perivascular spaces due to natalizumab,” Archives of Neurology, vol. 65, no. 12, pp. 1596–1603, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. C. de Andrés, R. Teijeiro, B. Alonso et al., “Long-term decrease in VLA-4 expression and functional impairment of dendritic cells during natalizumab therapy in patients with multiple sclerosis,” PLoS ONE, vol. 7, no. 4, Article ID e34103, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. V. Brinkmann, A. Billich, T. Baumruker et al., “Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis,” Nature Reviews Drug Discovery, vol. 9, no. 11, pp. 883–897, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. L. Kappos, E.-W. Radue, P. O'Connor et al., “A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis,” The New England Journal of Medicine, vol. 362, no. 5, pp. 387–401, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. L. Tar and L. Vécsei, “Fingolimod therapy in multiple sclerosis—the issue of the pathomechanism,” Ideggyógyászati Szemle, vol. 65, no. 3-4, pp. 83–100, 2012. View at Google Scholar · View at Scopus
  92. H. Müller, S. Hofer, N. Kaneider et al., “The immunomodulator FTY720 interferes with effector functions of human monocyte-derived dendritic cells,” European Journal of Immunology, vol. 35, no. 2, pp. 533–545, 2005. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. Y. Lan, A. De Creus, B. L. Colvin et al., “The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking In Vivo,” American Journal of Transplantation, vol. 5, no. 11, pp. 2649–2659, 2005. View at Publisher · View at Google Scholar · View at Scopus
  94. B. A. Durafourt, C. Lambert, T. A. Johnson, M. Blain, A. Bar-Or, and J. P. Antel, “Differential responses of human microglia and blood-derived myeloid cells to FTY720,” Journal of Neuroimmunology, vol. 230, no. 1-2, pp. 10–16, 2011. View at Publisher · View at Google Scholar · View at Scopus
  95. T. Vollmer, T. Stewart, and N. Baxter, “Mitoxantrone and cytotoxic drugs' mechanisms of action,” Neurology, vol. 74, supplement 1, pp. S41–S46, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. O. Neuhaus, H. Wiendl, B. C. Kieseier et al., “Multiple sclerosis: mitoxantrone promotes differential effects on immunocompetent cells in vitro,” Journal of Neuroimmunology, vol. 168, no. 1-2, pp. 128–137, 2005. View at Publisher · View at Google Scholar · View at Scopus
  97. J. M. Li, Y. Yang, P. Zhu, F. Zheng, F. L. Gong, and Y. W. Mei, “Mitoxantrone exerts both cytotoxic and immunoregulatory effects on activated microglial cells,” Immunopharmacology and Immunotoxicology, vol. 34, no. 1, pp. 36–41, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. A. Aldinucci, T. Biagioli, C. Manuelli, A. M. Repice, L. Massacesi, and C. Ballerini, “Modulating dendritic cells (DC) from immunogenic to tolerogenic responses: A novel mechanism of AZA/6-MP,” Journal of Neuroimmunology, vol. 218, no. 1-2, pp. 28–35, 2010. View at Publisher · View at Google Scholar · View at Scopus
  99. A. Haghikia and R. Gold, “Multiple sclerosis: TOWER confirms the efficacy of oral teriflunomide in MS,” Nature Reviews Neurology, vol. 10, no. 4, pp. 183–184, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. A. Sartori, D. Carle, and M. S. Freedman, “Teriflunomide: a novel oral treatment for relapsing multiple sclerosis,” Expert Opinion on Pharmacotherapy, vol. 15, no. 7, pp. 1019–1027, 2014. View at Publisher · View at Google Scholar · View at Scopus
  101. A. E. Miller, J. S. Wolinsky, L. Kappos et al., “Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial,” The Lancet Neurology, vol. 13, no. 10, pp. 977–986, 2014. View at Publisher · View at Google Scholar
  102. C. Warnke, G. M. zu Hörste, H.-P. Hartung, O. Stüve, and B. C. Kieseier, “Review of teriflunomide and its potential in the treatment of multiple sclerosis,” Neuropsychiatric Disease and Treatment, vol. 5, no. 1, pp. 333–340, 2009. View at Google Scholar · View at Scopus
  103. L. Li, J. Liu, T. Delohery, D. Zhang, C. Arendt, and C. Jones, “The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro,” Journal of Neuroimmunology, vol. 265, no. 1-2, pp. 82–90, 2013. View at Publisher · View at Google Scholar · View at Scopus
  104. P. Dimitrova, A. Skapenko, M. L. Herrmann, R. Schleyerbach, J. R. Kalden, and H. Schulze-Koops, “Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiation,” Journal of Immunology, vol. 169, no. 6, pp. 3392–3399, 2002. View at Publisher · View at Google Scholar · View at Scopus
  105. L. Li, J. Liu, D. Zhang, and C. Jones, “Teriflunomide treatment of human monocyte-derived dendritic cells in vitro does not impair their maturation or ability to induce allogeneic T-cell responses,” Multiple Sclerosis Journal, vol. 18, pp. 436–437, 2012. View at Google Scholar
  106. J. V. Venci and M. A. Gandhi, “Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis,” Annals of Pharmacotherapy, vol. 47, no. 12, pp. 1697–1702, 2013. View at Publisher · View at Google Scholar
  107. R. H. Scannevin, S. Chollate, M.-Y. Jung et al., “Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the nuclear factor (erythroid-derived 2)-like 2 pathway,” Journal of Pharmacology and Experimental Therapeutics, vol. 341, no. 1, pp. 274–284, 2012. View at Publisher · View at Google Scholar · View at Scopus
  108. H. Peng, M. Guerau-de-Arellano, V. B. Mehta et al., “Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor κB (NF-κB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling,” The Journal of Biological Chemistry, vol. 287, no. 33, pp. 28017–28026, 2012. View at Publisher · View at Google Scholar · View at Scopus
  109. K. Ghoreschi, J. Bruck, C. Kellereret et al., “Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells,” The Journal of Experimental Medicine, vol. 208, no. 11, pp. 2291–2303, 2011. View at Google Scholar
  110. W. Brück and C. Wegner, “Insight into the mechanism of laquinimod action,” Journal of the Neurological Sciences, vol. 306, no. 1-2, pp. 173–179, 2011. View at Publisher · View at Google Scholar · View at Scopus
  111. V. Jolivel, F. Luessi, J. Masri et al., “Modulation of dendritic cell properties by laquinimod as a mechanism for modulating multiple sclerosis,” Brain, vol. 136, no. 4, pp. 1048–1066, 2013. View at Publisher · View at Google Scholar · View at Scopus
  112. G. Comi, D. Jeffery, L. Kappos et al., “Placebo-controlled trial of oral laquinimod for multiple sclerosis,” The New England Journal of Medicine, vol. 366, no. 11, pp. 1000–1009, 2012. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Filippi, M. A. Rocca, E. Pagani et al., “Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 85, no. 8, pp. 851–858, 2014. View at Google Scholar
  114. T. L. Vollmer, P. S. Sorensen, K. Selmaj et al., “A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis,” Journal of Neurology, vol. 261, no. 4, pp. 773–783, 2014. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Martin, “Anti-CD25 (daclizumab) monoclonal antibody therapy in relapsing-remitting multiple sclerosis,” Clinical Immunology, vol. 142, no. 1, pp. 9–14, 2012. View at Publisher · View at Google Scholar · View at Scopus
  116. R. Gold, G. Giovannoni, K. Selmaj et al., “Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial,” The Lancet, vol. 381, no. 9884, pp. 2167–2175, 2013. View at Publisher · View at Google Scholar · View at Scopus
  117. H. Wiendl and C. C. Gross, “Modulation of IL-2Rα with daclizumab for treatment of multiple sclerosis,” Nature Reviews Neurology, vol. 9, no. 7, pp. 394–404, 2013. View at Publisher · View at Google Scholar · View at Scopus
  118. K. Mnasria, C. Lagaraine, F. Velge-Roussel, R. Oueslati, Y. Lebranchu, and C. Baron, “Anti-CD25 antibodies affect cytokine synthesis pattern of human dendritic cells and decrease their ability to prime allogeneic CD4+ T cells,” Journal of Leukocyte Biology, vol. 84, no. 2, pp. 460–467, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. K. S. Schluns, “Window of opportunity for daclizumab,” Nature Medicine, vol. 17, no. 5, pp. 545–547, 2011. View at Publisher · View at Google Scholar · View at Scopus
  120. S. C. Wuest, J. H. Edwan, J. F. Martin et al., “A role for interleukin-2 trans-presentation in dendritic cell-mediated T cell activation in humans, as revealed by daclizumab therapy,” Nature Medicine, vol. 17, no. 5, pp. 604–609, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. L. Klotz, S. G. Meuth, and H. Wiendl, “Immune mechanisms of new therapeutic strategies in multiple sclerosis—a focus on alemtuzumab,” Clinical Immunology, vol. 142, no. 1, pp. 25–30, 2012. View at Publisher · View at Google Scholar · View at Scopus
  122. H.-P. Hartung, O. Aktas, and A. N. Boyko, “Alemtuzumab: a new therapy for active relapsing-remitting multiple sclerosis,” Multiple Sclerosis Journal, 2014. View at Publisher · View at Google Scholar
  123. R. A. Diaz, S. Doss, M. J. Burke, E. George, and A. I. Adler, “Alemtuzumab for relapsing-remitting multiple sclerosis,” The Lancet Neurology, vol. 13, no. 9, pp. 869–870, 2014. View at Publisher · View at Google Scholar
  124. G. Ratzinger, J. L. Reagan, G. Heller, K. J. Busam, and J. W. Young, “Differential CD52 expression by distinct myeloid dendritic cell subsets: implications for alemtuzumab activity at the level of antigen presentation in allogeneic graft-host interactions in transplantation,” Blood, vol. 101, no. 4, pp. 1422–1429, 2003. View at Publisher · View at Google Scholar · View at Scopus
  125. A. G. S. Buggins, G. J. Mufti, J. Salisbury et al., “Peripheral blood but not tissue dendritic cells express CD52 and are depleted by treatment with alemtuzumab,” Blood, vol. 100, no. 5, pp. 1715–1720, 2002. View at Google Scholar · View at Scopus
  126. B. M. Kirsch, M. Haidinger, M. Zeyda et al., “Alemtuzumab (Campath-1H) induction therapy and dendritic cells: impact on peripheral dendritic cell repertoire in renal allograft recipients,” Transplant Immunology, vol. 16, no. 3-4, pp. 254–257, 2006. View at Publisher · View at Google Scholar · View at Scopus
  127. E. Havrdová, A. Belova, A. Goloborodkoet et al., “Positive proof of concept of AIN457, an antibody against interleukin-17A, in relapsing-remitting multiple sclerosis,” Multiple Sclerosis Journal, vol. 18, p. 513, 2012. View at Google Scholar
  128. A. Deiß, I. Brecht, A. Haarmann, and M. Buttmann, “Treating multiple sclerosis with monoclonal antibodies: a 2013 update,” Expert Review of Neurotherapeutics, vol. 13, no. 3, pp. 313–335, 2013. View at Publisher · View at Google Scholar · View at Scopus
  129. J. A. Hamilton, “Colony-stimulating factors in inflammation and autoimmunity,” Nature Reviews Immunology, vol. 8, no. 7, pp. 533–544, 2008. View at Publisher · View at Google Scholar · View at Scopus
  130. M. Ichikawa, C. S. Koh, A. Inoue et al., “Anti-IL-12 antibody prevents the development and progression of multiple sclerosis-like relapsing-remitting demyelinating disease in NOD mice induced with myelin oligodendrocyte glycoprotein peptide,” Journal of Neuroimmunology, vol. 102, no. 1, pp. 56–66, 2000. View at Publisher · View at Google Scholar · View at Scopus
  131. C. S. Constantinescu, M. Wysocka, B. Hilliard et al., “Antibodies against IL-12 prevent superantigen-induced and spontaneous relapses of experimental autoimmune encephalomyelitis,” Journal of Immunology, vol. 161, no. 9, pp. 5097–5104, 1998. View at Google Scholar · View at Scopus
  132. H. P. M. Brok, M. van Meurs, E. Blezer et al., “Prevention of experimental autoimmune encephalomyelitis in common marmosets using an anti-IL-12p40 monoclonal antibody,” The Journal of Immunology, vol. 169, no. 11, pp. 6554–6563, 2002. View at Publisher · View at Google Scholar · View at Scopus
  133. B. A. 't Hart, H. P. M. Brok, E. Remarque et al., “Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody,” The Journal of Immunology, vol. 175, no. 7, pp. 4761–4768, 2005. View at Publisher · View at Google Scholar · View at Scopus
  134. L. H. Kasper, D. Everitt, T. P. Leistet et al., “A phase I trial of an interleukin12/23 monoclonal antibody in relapsing multiple sclerosis,” Current Medical Research & Opinion, vol. 22, no. 9, pp. 1671–1678, 2006. View at Publisher · View at Google Scholar
  135. B. M. Segal, C. S. Constantinescu, A. Raychaudhuri, L. Kim, R. Fidelus-Gort, and L. H. Kasper, “Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study,” The Lancet Neurology, vol. 7, no. 9, pp. 796–804, 2008. View at Publisher · View at Google Scholar · View at Scopus
  136. T. L. Vollmer, D. R. Wynn, S. M. Alam, and J. Valdes, “A phase 2, 24-week, randomized, placebo-controlled, double-blind study examining the efficacy and safety of an anti-interleukin-12 and -23 monoclonal antibody in patients with relapsing-remitting or secondary progressive multiple sclerosis,” Multiple Sclerosis, vol. 17, no. 2, pp. 181–191, 2011. View at Publisher · View at Google Scholar · View at Scopus
  137. W. J. Trooster, A. W. Teelken, J. Kampinga, J. G. Loof, P. Nieuwenhuis, and J. M. Minderhoud, “Suppression of acute experimental allergic encephalomyelitis by the synthetic sex hormone 17-alpha-ethinylestradiol: an immunological study in the Lewis rat,” International Archives of Allergy and Immunology, vol. 102, no. 2, pp. 133–140, 1993. View at Publisher · View at Google Scholar · View at Scopus
  138. L. Jansson, T. Olsson, and R. Holmdahl, “Estrogen induces a potent suppression of experimental autoimmune encephalomyelitis and collagen-induced arthritis in mice,” Journal of Neuroimmunology, vol. 53, no. 2, pp. 203–207, 1994. View at Publisher · View at Google Scholar · View at Scopus
  139. H. Y. Liu, A. C. Buenafe, A. Matejuk et al., “Estrogen inhibition of EAE involves effects on dendritic cell function,” Journal of Neuroscience Research, vol. 70, no. 2, pp. 238–248, 2002. View at Publisher · View at Google Scholar · View at Scopus
  140. Q.-H. Zhang, Y.-Z. Hu, J. Cao, Y.-Q. Zhong, Y.-F. Zhao, and Q.-B. Mei, “Estrogen influences the differentiation, maturation and function of dendritic cells in rats with experimental autoimmune encephalomyelitis,” Acta Pharmacologica Sinica, vol. 25, no. 4, pp. 508–513, 2004. View at Google Scholar · View at Scopus
  141. A. Pettersson, C. Ciumas, V. Chirsky, H. Link, Y.-M. Huang, and B.-G. Xiao, “Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis,” Journal of Neuroimmunology, vol. 156, no. 1-2, pp. 58–65, 2004. View at Publisher · View at Google Scholar · View at Scopus
  142. W.-H. Zhu, C.-Z. Lu, Y.-M. Huang, H. Link, and B.-G. Xiao, “A putative mechanism on remission of multiple sclerosis during pregnancy: estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells,” Multiple Sclerosis, vol. 13, no. 1, pp. 33–40, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. S. Du, F. Sandoval, P. Trinh, E. Umeda, and R. Voskuhl, “Estrogen receptor-beta ligand treatment modulates dendritic cells in the target organ during autoimmune demyelinating disease,” European Journal of Immunology, vol. 41, no. 1, pp. 140–150, 2011. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Simpson Jr., L. Blizzard, P. Otahal, I. van der Mei, and B. Taylor, “Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis,” Journal of Neurology, Neurosurgery & Psychiatry, vol. 82, no. 10, pp. 1132–1141, 2011. View at Publisher · View at Google Scholar · View at Scopus
  145. S. Hewer, R. Lucas, I. van der Mei, and B. V. Taylor, “Vitamin D and multiple sclerosis,” Journal of Clinical Neuroscience, vol. 20, no. 5, pp. 634–641, 2013. View at Publisher · View at Google Scholar · View at Scopus
  146. J. Correale, M. C. Ysrraelit, and M. I. Gaitn, “Immunomodulatory effects of Vitamin D in multiple sclerosis,” Brain, vol. 132, no. 5, pp. 1146–1160, 2009. View at Publisher · View at Google Scholar · View at Scopus
  147. H.-L. Zhang and J. Wu, “Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis,” Neuroscience Bulletin, vol. 26, no. 6, pp. 445–454, 2010. View at Publisher · View at Google Scholar · View at Scopus
  148. L. Piemonti, P. Monti, M. Sironi et al., “Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells,” Journal of Immunology, vol. 164, no. 9, pp. 4443–4451, 2000. View at Publisher · View at Google Scholar · View at Scopus
  149. H. Bartosik-Psujek, J. Tabarkiewicz, K. Pocinska, Z. Stelmasiak, and J. Rolinski, “Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis,” Multiple Sclerosis, vol. 16, no. 12, pp. 1513–1516, 2010. View at Publisher · View at Google Scholar · View at Scopus
  150. D. Raϊch-Regué, L. Grau-López, M. Naranjo-Gómez et al., “Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients,” European Journal of Immunology, vol. 42, no. 3, pp. 771–782, 2012. View at Publisher · View at Google Scholar
  151. A. S. Farias, G. S. Spagnol, P. Bordeaux-Rego et al., “Vitamin D3 induces IDO+ tolerogenic DCs and enhances Treg, reducing the severity of EAE,” CNS Neuroscience and Therapeutics, vol. 19, no. 4, pp. 269–277, 2013. View at Publisher · View at Google Scholar · View at Scopus
  152. J. M. Burton, S. Kimball, R. Vieth et al., “A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis,” Neurology, vol. 74, no. 23, pp. 1852–1859, 2010. View at Publisher · View at Google Scholar · View at Scopus
  153. G. Mosayebi, A. Ghazavi, K. Ghasami, Y. Jand, and P. Kokhaei, “Therapeutic effect of vitamin D3 in multiple sclerosis patients,” Immunological Investigations, vol. 40, no. 6, pp. 627–639, 2011. View at Publisher · View at Google Scholar · View at Scopus
  154. R. Kushwah and J. Hu, “Role of dendritic cells in the induction of regulatory T cells,” Cell and Bioscience, vol. 1, no. 1, article 20, 2011. View at Publisher · View at Google Scholar · View at Scopus
  155. D. M. Mosser and X. Zhang, “Interleukin-10: new perspectives on an old cytokine,” Immunological Reviews, vol. 226, no. 1, pp. 205–218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  156. S. B. Adikari, A. Petterssor, M. Soderstrom, Y.-M. Huang, and H. Link, “Interleukin-10-modulated immature dendritic cells control the proinflammatory environment in multiple sclerosis,” Scandinavian Journal of Immunology, vol. 59, no. 6, pp. 600–606, 2004. View at Publisher · View at Google Scholar · View at Scopus
  157. G. Perona-Wright, S. M. Anderton, S. E. M. Howie, and D. Gray, “IL-10 permits transient activation of dendritic cells to tolerize T cells and protect from central nervous system autoimmune disease,” International Immunology, vol. 19, no. 9, pp. 1123–1134, 2007. View at Publisher · View at Google Scholar · View at Scopus
  158. R. Matsuda, T. Kezuka, C. Nishiyama et al., “Interleukin-10 gene-transfected mature dendritic cells suppress murine experimental autoimmune optic neuritis,” Investigative Ophthalmology and Visual Science, vol. 53, no. 11, pp. 7235–7245, 2012. View at Publisher · View at Google Scholar · View at Scopus
  159. S. Gregori, D. Tomasoni, V. Pacciani et al., “Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway,” Blood, vol. 116, no. 6, pp. 935–944, 2010. View at Publisher · View at Google Scholar
  160. G. Amodio and S. Gregori, “Human tolerogenic DC-10: perspectives for clinical applications,” Transplantation Research, vol. 1, no. 1, article 14, 2012. View at Publisher · View at Google Scholar
  161. M. Ishikawa, Y. Jin, H. Guo, H. Link, and B.-G. Xiao, “Nasal administration of transforming growth factor-β1, induces dendritic cells and inhibits protracted-relapsing experimental allergic encephalomyelitis,” Multiple Sclerosis, vol. 5, no. 3, pp. 184–191, 1999. View at Google Scholar · View at Scopus
  162. Y.-X. Jin, L.-Y. Xu, H. Guo, M. Ishikawa, H. Link, and B.-G. Xiao, “TGF-β1 inhibits protracted-relapsing experimental autoimmune encephalomyelitis by activating dendritic cells,” Journal of Autoimmunity, vol. 14, no. 3, pp. 213–220, 2000. View at Publisher · View at Google Scholar · View at Scopus
  163. B. G. Xiao, W. H. Zhu, and C. Z. Lu, “The presence of GM-CSF and IL-4 interferes with effect of TGF-beta1 on antigen presenting cells in patients with multiple sclerosis and in rats with experimental autoimmune encephalomyelitis,” Cellular Immunology, vol. 249, no. 1, pp. 30–36, 2007. View at Publisher · View at Google Scholar · View at Scopus
  164. A. C. Melton, S. L. Bailey-Bucktrout, M. A. Travis, B. T. Fife, J. A. Bluestone, and D. Sheppard, “Expression of αvβ8 integrin on dendritic cells regulates Th17 cell development and experimental autoimmune encephalomyelitis in mice,” The Journal of Clinical Investigation, vol. 120, no. 12, pp. 4436–4444, 2010. View at Publisher · View at Google Scholar · View at Scopus
  165. M. Acharya, S. Mukhopadhyay, H. Païdassi et al., “αv Integrin expression by DCs is required for Th17 cell differentiation and development of experimental autoimmune encephalomyelitis in mice,” The Journal of Clinical Investigation, vol. 120, no. 12, pp. 4445–4452, 2010. View at Publisher · View at Google Scholar · View at Scopus
  166. C. L. Langrish, Y. Chen, W. M. Blumenschein et al., “IL-23 drives a pathogenic T cell population that induces autoimmune inflammation,” The Journal of Experimental Medicine, vol. 201, no. 2, pp. 233–240, 2005. View at Publisher · View at Google Scholar
  167. Y. Komiyama, S. Nakae, T. Matsuki et al., “IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis,” Journal of Immunology, vol. 177, no. 1, pp. 566–573, 2006. View at Publisher · View at Google Scholar · View at Scopus
  168. H. H. Hofstetter, S. M. Ibrahim, D. Koczan et al., “Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis,” Cellular Immunology, vol. 237, no. 2, pp. 123–130, 2005. View at Publisher · View at Google Scholar · View at Scopus
  169. S. Haak, A. L. Croxford, K. Kreymborg et al., “IL-17A and IL-17F do not contribute vitally to autoimmune neuro-inflammation in mice,” Journal of Clinical Investigation, vol. 119, no. 1, pp. 61–69, 2009. View at Publisher · View at Google Scholar · View at Scopus
  170. B. Becher and B. M. Segal, “TH17 cytokines in autoimmune neuro-inflammation,” Current Opinion in Immunology, vol. 23, no. 6, pp. 707–712, 2011. View at Publisher · View at Google Scholar · View at Scopus
  171. K. Kreymborg, R. Etzensperger, L. Dumoutier et al., “IL-22 is expressed by Th17 cells in an IL-23-dependent fashion, but not required for the development of autoimmune encephalomyelitis,” The Journal of Immunology, vol. 179, no. 12, pp. 8098–8104, 2007. View at Publisher · View at Google Scholar · View at Scopus
  172. J. M. Coquet, S. Chakravarti, M. J. Smyth, and D. I. Godfrey, “Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis,” The Journal of Immunology, vol. 180, no. 11, pp. 7097–7101, 2008. View at Publisher · View at Google Scholar · View at Scopus
  173. I. Sonderegger, J. Kisielow, R. Meier, C. King, and M. Kopf, “IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo,” European Journal of Immunology, vol. 38, no. 7, pp. 1833–1838, 2008. View at Publisher · View at Google Scholar · View at Scopus
  174. B. Almolda, M. Costa, M. Montoya, B. González, and B. Castellano, “Increase in th17 and t-reg lymphocytes and decrease of il22 correlate with the recovery phase of acute eae in rat,” PLoS ONE, vol. 6, no. 11, Article ID e27473, 2011. View at Publisher · View at Google Scholar · View at Scopus
  175. W. Xu, R. Y. Li, Y. Dai et al., “IL-22 secreting CD4+ T cells in the patients with neuromyelitis optica and multiple sclerosis,” Journal of Neuroimmunology, vol. 261, no. 1-2, pp. 87–91, 2013. View at Publisher · View at Google Scholar
  176. C. Sutton, C. Brereton, B. Keogh, K. H. G. Mills, and E. C. Lavelle, “A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis,” Journal of Experimental Medicine, vol. 203, no. 7, pp. 1685–1691, 2006. View at Publisher · View at Google Scholar · View at Scopus
  177. Q. Li, N. Powell, H. Zhang et al., “Endothelial IL-1R1 is a critical mediator of EAE pathogenesis,” Brain, Behavior, and Immunity, vol. 25, no. 1, pp. 160–167, 2011. View at Publisher · View at Google Scholar · View at Scopus
  178. B. Cannella and C. S. Raine, “The adhesion molecule and cytokine profile of multiple sclerosis lesions,” Annals of Neurology, vol. 37, no. 4, pp. 424–435, 1995. View at Publisher · View at Google Scholar · View at Scopus
  179. M. El-Behi, B. Ciric, H. Dai et al., “The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF,” Nature Immunology, vol. 12, no. 6, pp. 568–575, 2011. View at Publisher · View at Google Scholar · View at Scopus
  180. L. Codarri, G. Gyülvészii, V. Tosevski et al., “RORγ3t drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation,” Nature Immunology, vol. 12, no. 6, pp. 560–567, 2011. View at Publisher · View at Google Scholar · View at Scopus
  181. I. L. King, M. A. Kroenke, and B. M. Segal, “GM-CSF-dependent, CD103+ dermal dendritic cells play a critical role in Th effector cell differentiation after subcutaneous immunization,” Journal of Experimental Medicine, vol. 207, no. 5, pp. 953–961, 2010. View at Publisher · View at Google Scholar · View at Scopus
  182. M. Grell, H. Wajant, G. Zimmermann, and P. Scheurich, “The type 1 receptor (CD120a) is the high-affinity receptor for soluble tumor necrosis factor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 2, pp. 570–575, 1998. View at Publisher · View at Google Scholar · View at Scopus
  183. N. H. Ruddle, C. M. Bergman, K. M. McGrath et al., “An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis,” The Journal of Experimental Medicine, vol. 172, no. 4, pp. 1193–1200, 1990. View at Publisher · View at Google Scholar · View at Scopus
  184. G. C. Suvannavejh, H. O. Lee, J. Padilla, M. C. Dal Canto, T. A. Barrett, and S. D. Miller, “Divergent roles for p55 and p75 tumor necrosis factor receptors in the pathogenesis of MOG35-55-induced experimental autoimmune encephalomyelitis,” Cellular Immunology, vol. 205, no. 1, pp. 24–33, 2000. View at Publisher · View at Google Scholar · View at Scopus
  185. H. Körner, F. A. Lemckert, G. Chaudhri, S. Etteldorf, and J. D. Sedgwick, “Tumor necrosis factor blockade in actively induced experimental autoimmune encephalomyelitis prevents clinical disease despite activated T cell infiltration to the central nervous system,” European Journal of Immunology, vol. 27, no. 8, pp. 1973–1981, 1997. View at Publisher · View at Google Scholar · View at Scopus
  186. A. Caminero, M. Comabella, and X. Montalban, “Tumor necrosis factor alpha (TNF-α), anti-TNF-α and demyelination revisited: an ongoing story,” Journal of Neuroimmunology, vol. 234, no. 1-2, pp. 1–6, 2011. View at Publisher · View at Google Scholar · View at Scopus
  187. B. W. Van Oosten, F. Barkhof, L. Truyen et al., “Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2,” Neurology, vol. 47, no. 6, pp. 1531–1534, 1996. View at Publisher · View at Google Scholar · View at Scopus
  188. E. B. Samoilova, J. L. Horton, B. Hilliard, T.-S. T. Liu, and Y. Chen, “IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells,” The Journal of Immunology, vol. 161, no. 12, pp. 6480–6486, 1998. View at Google Scholar · View at Scopus
  189. S. Serada, M. Fujimoto, M. Mihara et al., “IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 26, pp. 9041–9046, 2008. View at Publisher · View at Google Scholar · View at Scopus
  190. M. D. Leech, T. A. Barr, D. G. Turner et al., “Cutting edge: IL-6-Dependent autoimmune disease: dendritic cells as a sufficient, but transient, source,” Journal of Immunology, vol. 190, no. 3, pp. 881–885, 2013. View at Publisher · View at Google Scholar · View at Scopus
  191. D. Maimone, G. C. Guazzi, and P. Annunziata, “IL-6 detection in multiple sclerosis brain,” Journal of the Neurological Sciences, vol. 146, no. 1, pp. 59–65, 1997. View at Publisher · View at Google Scholar · View at Scopus
  192. B. C. Kieseier, O. Stüve, T. Dehmel et al., “Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses,” JAMA Neurology, vol. 70, no. 3, pp. 390–393, 2013. View at Publisher · View at Google Scholar
  193. M. Menges, S. Rößner, C. Voigtländer et al., “Repetitive injections of dendritic cells matured with tumor necrosis factor α induce antigen-specific protection of mice from autoimmunity,” The Journal of Experimental Medicine, vol. 195, no. 1, pp. 15–21, 2002. View at Publisher · View at Google Scholar · View at Scopus
  194. S. Hirata, S. Senju, H. Matsuyoshi, D. Fukuma, Y. Uemura, and Y. Nishimura, “Prevention of experimental autoimmune encephalomyelitis by transfer of embryonic stem cell-derived dendritic cells expressing myelin oligodendrocyte glycoprotein peptide along with TRAIL or programmed death-1 ligand 1,” Journal of Immunology, vol. 174, no. 4, pp. 1888–1897, 2005. View at Publisher · View at Google Scholar · View at Scopus
  195. R. Thomé, L. K. Issayama, R. Digangi et al., “Dendritic cells treated with chloroquine modulate experimental autoimmune encephalomyelitis,” Immunology and Cell Biology, vol. 92, no. 2, pp. 124–132, 2014. View at Publisher · View at Google Scholar · View at Scopus
  196. F. Zhou, B. Ciric, G.-X. Zhang, and A. Rostami, “Immunotherapy using lipopolysaccharide-stimulated bone marrow-derived dendritic cells to treat experimental autoimmune encephalomyelitis,” Clinical & Experimental Immunology, vol. 178, no. 3, pp. 447–458, 2014. View at Publisher · View at Google Scholar
  197. F. Zhou, E. Lauretti, A. di Meco et al., “Intravenous transfer of apoptotic cell-treated dendritic cells leads to immune tolerance by blocking Th17 cell activity,” Immunobiology, vol. 218, no. 8, pp. 1069–1076, 2013. View at Publisher · View at Google Scholar · View at Scopus
  198. M. Isaksson, B. Ardesjö, L. Rönnblom et al., “Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE,” European Journal of Immunology, vol. 39, no. 10, pp. 2925–2935, 2009. View at Publisher · View at Google Scholar · View at Scopus