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Nat Neurosci. 2017 May;20(5):674-680. doi: 10.1038/nn.4528. Epub 2017 Mar 13.

Regulatory T cells promote myelin regeneration in the central nervous system.

Author information

1
Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
2
Department of Neurology and Program in Neurosciences, University of California, San Francisco, California, USA.
3
Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
4
Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, UK.
5
Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
6
Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Ireland.
7
Université Côte d'Azur, CNRS, GREDEG, Nice, France.
8
International CCN Society, Paris, France.

Abstract

Regeneration of CNS myelin involves differentiation of oligodendrocytes from oligodendrocyte progenitor cells. In multiple sclerosis, remyelination can fail despite abundant oligodendrocyte progenitor cells, suggesting impairment of oligodendrocyte differentiation. T cells infiltrate the CNS in multiple sclerosis, yet little is known about T cell functions in remyelination. We report that regulatory T cells (Treg) promote oligodendrocyte differentiation and (re)myelination. Treg-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of Treg. In brain slice cultures, Treg accelerated developmental myelination and remyelination, even in the absence of overt inflammation. Treg directly promoted oligodendrocyte progenitor cell differentiation and myelination in vitro. We identified CCN3 as a Treg-derived mediator of oligodendrocyte differentiation and myelination in vitro. These findings reveal a new regenerative function of Treg in the CNS, distinct from immunomodulation. Although the cells were originally named 'Treg' to reflect immunoregulatory roles, this also captures emerging, regenerative Treg functions.

PMID:
28288125
PMCID:
PMC5409501
DOI:
10.1038/nn.4528
[Indexed for MEDLINE]
Free PMC Article

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