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The role of regulatory T cells in multiple sclerosis

Abstract

The dysregulation of inflammatory responses and of immune self-tolerance is considered to be a key element in the autoreactive immune response in multiple sclerosis (MS). Regulatory T (TREG) cells have emerged as crucial players in the pathogenetic scenario of CNS autoimmune inflammation. Targeted deletion of TREG cells causes spontaneous autoimmune disease in mice, whereas augmentation of TREG-cell function can prevent the development of or alleviate variants of experimental autoimmune encephalomyelitis, the animal model of MS. Recent findings indicate that MS itself is also accompanied by dysfunction or impaired maturation of TREG cells. The development and function of TREG cells is closely linked to dendritic cells (DCs), which have a central role in the activation and reactivation of encephalitogenic cells in the CNS. DCs and TREG cells have an intimate bidirectional relationship, and, in combination with other factors and cell types, certain types of DCs are capable of inducing TREG cells. Consequently, TREG cells and DCs have been recognized as potential therapeutic targets in MS. This Review compiles the current knowledge on the role and function of various subsets of TREG cells in MS and experimental autoimmune encephalomyelitis. We also highlight the role of tolerogenic DCs and their bidirectional interaction with TREG cells during CNS autoimmunity.

Key Points

  • Multiple sclerosis (MS) is considered to be a T-cell-mediated autoimmune disease

  • Regulatory T (TREG) cells and dendritic cells (DCs) represent distinct cell populations that are capable of maintaining the quality of immune responses, and these cells could be a novel target for the treatment of MS

  • TREG cells are classified according to their surface phenotype and cytokine secretion profile, and whether they are naturally occurring or inducible

  • DCs can modulate the expansion and function of TREG cells during CNS inflammation; DCs with this type of function are known as 'tolerogenic' DCs

  • MS seems to be associated with the dysfunction or impaired maturation of certain TREG-cell and DC populations

  • New therapies for CNS autoimmune diseases that employ the modulation of TREG-cell and DC functions are a promising avenue of research

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Figure 1: Homeostasis of CNS immunity.
Figure 2: The influence of human dendritic cell subsets on the generation of effector and regulatory T cells.
Figure 3: Balance between immunogenic and tolerogenic mechanisms in multiple sclerosis: a hypothesis.

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Acknowledgements

H Wiendl is supported by the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Thyssen Foundation and the German MS Society.

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Correspondence to Heinz Wiendl.

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Zozulya, A., Wiendl, H. The role of regulatory T cells in multiple sclerosis. Nat Rev Neurol 4, 384–398 (2008). https://doi.org/10.1038/ncpneuro0832

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