Journal of Molecular Medicine

, Volume 88, Issue 6, pp 535–544

The role of dendritic cells in CNS autoimmunity

  • Alla L. Zozulya
  • Benjamin D. Clarkson
  • Sonja Ortler
  • Zsuzsanna Fabry
  • Heinz Wiendl
Review

DOI: 10.1007/s00109-010-0607-4

Cite this article as:
Zozulya, A.L., Clarkson, B.D., Ortler, S. et al. J Mol Med (2010) 88: 535. doi:10.1007/s00109-010-0607-4
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Abstract

Multiple sclerosis (MS) is a chronic immune-mediated, central nervous system (CNS) demyelinating disease. Clinical and histopathological features suggest an inflammatory etiology involving resident CNS innate cells as well as invading adaptive immune cells. Encephalitogenic myelin-reactive T cells have been implicated in the initiation of an inflammatory cascade, eventually resulting in demyelination and axonal damage (the histological hallmarks of MS). Dendritic cells (DC) have recently emerged as key modulators of this immunopathological cascade, as supported by studies in humans and experimental disease models. In one such model, experimental autoimmune encephalomyelitis (EAE), CNS microvessel-associated DC have been shown to be essential for local antigen recognition by myelin-reactive T cells. Moreover, the functional state and compartmental distribution of DC derived from CNS and associated lymphatics seem to be limiting factors in both the induction and effector phases of EAE. Moreover, DC modulate and balance the recruitment of encephalitogenic and regulatory T cells into CNS tissue. This capacity is critically influenced by DC surface expression of co-stimulatory or co-inhibitory molecules. The fact that DC accumulate in the CNS before T cells and can direct T-cell responses suggests that they are key determinants of CNS autoimmune outcomes. Here we provide a comprehensive review of recent advances in our understanding of CNS-derived DC and their relevance to neuroinflammation.

Keywords

Dendritic cellsT-cell immune responsesMultiple sclerosisExperimental autoimmune encephalomyelitisCNSCo-inhibitory moleculesB7-H1PD-L1

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Alla L. Zozulya
    • 1
  • Benjamin D. Clarkson
    • 2
  • Sonja Ortler
    • 3
  • Zsuzsanna Fabry
    • 2
  • Heinz Wiendl
    • 3
  1. 1.Department of ImmunologyUniversity of GenevaGenèveSwitzerland
  2. 2.Department of Pathology and Laboratory MedicineUniversity of Wisconsin-MadisonMadisonUSA
  3. 3.Department of Neurology, Clinical Research Group for MS and NeuroimmunologyUniversity of WuerzburgWuerzburgGermany