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The role of dendritic cells in multiple sclerosis

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Abstract

Although multiple sclerosis (MS) is a presumed T-cell-mediated disease, it is unclear what triggers the development of neuroantigen-specific T cells. Autoreactive CD4+ T cells are activated by antigen presenting cells; dendritic cells (DCs) are the primary antigen presenting cells directing T-cell functions and are, therefore, extremely important in directing the immune pathology characteristic of MS. Three important concepts have emerged regarding DCs in MS. First, DCs are present within the healthy central nervous system (CNS) in association with the cerebrospinal fluid space and microvasculature. Therefore, the potential for sampling of CNS antigens in similar fashion to other tissues and organs exists and likely plays an integral role in CNS immunity. The degree of involvement, as well as the source, of these CNS DCs has been addressed by several studies using the experimental autoimmune encephalomyelitis animal model. Second, DCs are found within MS lesions and have been shown to be functionally abnormal in patients with MS. Lastly, therapeutics directed at DCs could potentially be engineered for treatment in MS and in fact may already be involved in the mechanisms of current immunomodulatory therapies.

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References and Recommended Reading

  1. Hafler DA: Multiple sclerosis. J Clin Invest 2004, 113:788–794.

    Article  PubMed  CAS  Google Scholar 

  2. Weiner HL: Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol 2004, 61:1613–1615.

    Article  PubMed  Google Scholar 

  3. Barcellos LF, Sawcer S, Ramsay PP, et al.: Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum Mol Genet 2006, 15:2813–2824.

    Article  PubMed  CAS  Google Scholar 

  4. Bettelli E, Carrier Y, Gao W, et al.: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006, 441:235–238.

    Article  PubMed  CAS  Google Scholar 

  5. Hardin JA: Dendritic cells: potential triggers of autoimmunity and targets for therapy. Ann Rheum Dis 2005, 64(Suppl 4):iv86–90.

    Article  PubMed  CAS  Google Scholar 

  6. Ransohoff RM, Kivisakk P, Kidd G: Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003, 3:569–581.

    Article  PubMed  CAS  Google Scholar 

  7. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998, 392:245–252.

    Article  PubMed  CAS  Google Scholar 

  8. Shortman K, Liu YJ: Mouse and human dendritic cell subtypes. Nat Rev Immunol 2002, 2:151–161.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Reis e Sousa C: Dendritic cells in a mature age. Nat Rev Immunol 2006, 6:476–483.

    Article  PubMed  CAS  Google Scholar 

  11. Dudziak D, Kamphorst AO, Heidkamp GF, et al.: Differential antigen processing by dendritic cell subsets in vivo. Science 2007, 315:107–111.

    Article  PubMed  CAS  Google Scholar 

  12. Fischer HG, Reichmann G: Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol 2001, 166:2717–2726.

    PubMed  CAS  Google Scholar 

  13. Matyszak MK, Perry VH: The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system. Neuroscience 1996, 74:599–608.

    Article  PubMed  CAS  Google Scholar 

  14. McMenamin PG: 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. J Comp Neurol 1999, 405:553–562.

    Article  PubMed  CAS  Google Scholar 

  15. McMenamin PG, Wealthall RJ, Deverall M, et al.: Macrophages and dendritic cells in the rat meninges and choroid plexus: three-dimensional localisation by environmental scanning electron microscopy and confocal microscopy. Cell Tissue Res 2003, 313:259–269.

    Article  PubMed  Google Scholar 

  16. Serafini B, Columba-Cabezas S, Di Rosa F, Aloisi F: Intracerebral recruitment and maturation of dendritic cells in the onset and progression of experimental autoimmune encephalomyelitis. Am J Pathol 2000, 157:1991–2002.

    PubMed  CAS  Google Scholar 

  17. Greter M, Heppner FL, Lemos MP, et al.: Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 2005, 11:328–334.

    Article  PubMed  CAS  Google Scholar 

  18. Nataf S, Strazielle N, Hatterer E, et al.: Rat choroid plexuses contain myeloid progenitors capable of differentiation toward macrophage or dendritic cell phenotypes. Glia 2006, 54:160–171.

    Article  PubMed  Google Scholar 

  19. Serafini B, Rosicarelli B, Magliozzi R, et al.: Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake, and interaction with proliferating T cells. J Neuropathol Exp Neurol 2006, 65:124–141.

    PubMed  CAS  Google Scholar 

  20. Hanly A, Petito CK: HLA-DR-positive dendritic cells of the normal human choroid plexus: a potential reservoir of HIV in the central nervous system. Hum Pathol 1998, 29:88–93.

    Article  PubMed  CAS  Google Scholar 

  21. Fabriek BO, Van Haastert ES, Galea I, et al.: CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia 2005, 51:297–305.

    Article  PubMed  Google Scholar 

  22. Williams K, Alvarez X, Lackner AA: Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 2001, 36:156–164.

    Article  PubMed  CAS  Google Scholar 

  23. Pashenkov M, Huang YM, Kostulas V, et al.: Two subsets of dendritic cells are present in human cerebrospinal fluid. Brain 2001, 124:480–492.

    Article  PubMed  CAS  Google Scholar 

  24. Kivisakk P, Mahad DJ, Callahan MK, et al.: Expression of CCR7 in multiple sclerosis: implications for CNS immunity. Ann Neurol 2004, 55:627–638.

    Article  PubMed  CAS  Google Scholar 

  25. Pashenkov M, Teleshova N, Kouwenhoven M, et al.: Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple sclerosis and acute optic neuritis. Clin Exp Immunol 2002, 127:519–526.

    Article  PubMed  CAS  Google Scholar 

  26. Plumb J, Armstrong MA, Duddy M, et al.: CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions. Mult Scler 2003, 9:142–147.

    Article  PubMed  CAS  Google Scholar 

  27. Li Y, Chu N, Hu A, et al.: Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain 2007, 130(pt 2):490–501.

    Article  PubMed  Google Scholar 

  28. Huang YM, Xiao BG, Ozenci V, et al.: Multiple sclerosis is associated with high levels of circulating dendritic cells secreting pro-inflammatory cytokines. J Neuroimmunol 1999, 99:82–90.

    Article  PubMed  CAS  Google Scholar 

  29. Karni A, Abraham M, Monsonego A, et al.: Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response. J Immunol 2006, 177:4196–4202.

    PubMed  CAS  Google Scholar 

  30. Vaknin-Dembinsky A, Balashov K, Weiner HL: IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J Immunol 2006, 176:7768–7774.

    PubMed  CAS  Google Scholar 

  31. Stasiolek M, Bayas A, Kruse N, et al.: Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis. Brain 2006, 129:1293–1305.

    Article  PubMed  Google Scholar 

  32. Lopez C, Comabella M, Al-Zayat H, et al.: Altered maturation of circulating dendritic cells in primary progressive MS patients. J Neuroimmunol 2006, 175:183–191.

    Article  PubMed  CAS  Google Scholar 

  33. Martin R, McFarland HF: Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis. Crit Rev Clin Lab Sci 1995, 32:121–182.

    PubMed  CAS  Google Scholar 

  34. Dittel BN, Visintin I, Merchant RM, Janeway CA Jr: Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis. J Immunol 1999, 163:32–39.

    PubMed  CAS  Google Scholar 

  35. Furtado GC, Pina B, Tacke F, et al.: A novel model of demyelinating encephalomyelitis induced by monocytes and dendritic cells. J Immunol 2006, 177:6871–6879.

    PubMed  CAS  Google Scholar 

  36. McMahon EJ, Bailey SL, Castenada CV, et al.: Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 2005, 11:335–339.

    Article  PubMed  CAS  Google Scholar 

  37. de Vos AF, van Meurs M, Brok HP, et al.: Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol 2002, 169:5415–5423.

    PubMed  Google Scholar 

  38. Bailey SL, Schreiner B, McMahon EJ, Miller SD: CNS myeloid DCs presenting endogenous myelin peptides ‘preferentially’ polarize CD4(+) T(H)-17 cells in relapsing EAE. Nat Immunol 2007, 8:172–180.

    Article  PubMed  CAS  Google Scholar 

  39. Suter T, Biollaz G, Gatto D, et al.: The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation. Eur J Immunol 2003, 33:2998–3006.

    Article  PubMed  CAS  Google Scholar 

  40. Hatterer E, Davoust N, Didier-Bazes M, et al.: How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes. Blood 2006, 107:806–812.

    Article  PubMed  CAS  Google Scholar 

  41. Karman J, Ling C, Sandor M, Fabry Z: Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol 2004, 173:2353–2361.

    PubMed  CAS  Google Scholar 

  42. Hickey WF, Kimura H: Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 1988, 239:290–292.

    Article  PubMed  CAS  Google Scholar 

  43. Platten M, Steinman L: Multiple sclerosis: trapped in deadly glue. Nat Med 2005, 11:252–253.

    Article  PubMed  CAS  Google Scholar 

  44. Ponomarev ED, Shriver LP, Maresz K, Dittel BN: Microglial cell activation and proliferation precedes the onset of CNS autoimmunity. J Neurosci Res 2005, 81:374–389.

    Article  PubMed  CAS  Google Scholar 

  45. Carson MJ, Doose JM, Melchior B, et al.: CNS immune privilege: hiding in plain sight. Immunol Rev 2006, 213:48–65.

    Article  PubMed  Google Scholar 

  46. Zang YC, Skinner SM, Robinson RR, et al.: Regulation of differentiation and functional properties of monocytes and monocyte-derived dendritic cells by interferon beta in multiple sclerosis. Mult Scler 2004, 10:499–506.

    Article  PubMed  Google Scholar 

  47. Schreiner B, Mitsdoerffer M, Kieseier BC, et al.: Interferon-beta 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. J Neuroimmunol 2004, 155:172–182.

    Article  PubMed  CAS  Google Scholar 

  48. Vieira PL, Heystek HC, Wormmeester J, et al.: Glatiramer acetate (copolymer-1, copaxone) promotes Th2 cell development and increased IL-10 production through modulation of dendritic cells. J Immunol 2003, 170:4483–4488.

    PubMed  CAS  Google Scholar 

  49. Whartenby KA, Calabresi PA, McCadden E, et al.: Inhibition of FLT3 signaling targets DCs to ameliorate autoimmune disease. Proc. Natl Acad Sci U S A 2005, 102:16741–16746.

    Article  PubMed  CAS  Google Scholar 

  50. Pettersson A, Wu XC, Ciumas C, et al.: CD8alpha dendritic cells and immune protection from experimental allergic encephalomyelitis. Clin Exp Immunol 2004, 137:486–495.

    Article  PubMed  CAS  Google Scholar 

  51. Liu HY, Buenafe AC, Matejuk A, et al.: Estrogen inhibition of EAE involves effects on dendritic cell function. J Neurosci Res 2002, 70:238–248.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, Hospital of the University of Pennsylvania, 745 BRB II/III, 421 Curie Boulevard, Philadelphia, PA, 19104, USA

    Gregory F. Wu MD, PhD

Authors
  1. Gregory F. Wu MD, PhD
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  2. Terri M. Laufer MD
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Correspondence to Gregory F. Wu MD, PhD.

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Wu, G.F., Laufer, T.M. The role of dendritic cells in multiple sclerosis. Curr Neurol Neurosci Rep 7, 245–252 (2007). https://doi.org/10.1007/s11910-007-0037-z

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