Regulatory T cells promote myelin regeneration in the central nervous system
Regeneration of myelin is a dynamic, yet enigmatic process. Dombrowski et al. uncover a central role for regulatory T (T reg ) cells in driving oligodendrocyte differentiation, in part via CCN3, a novel factor in T reg function and oligodendrocyte biology. This identifies T reg cells as key cellular...
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Published in | Nature neuroscience Vol. 20; no. 5; pp. 674 - 680 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.05.2017
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Regeneration of myelin is a dynamic, yet enigmatic process. Dombrowski
et al.
uncover a central role for regulatory T (T
reg
) cells in driving oligodendrocyte differentiation, in part via CCN3, a novel factor in T
reg
function and oligodendrocyte biology. This identifies T
reg
cells as key cellular players in efficient remyelination.
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 (T
reg
) promote oligodendrocyte differentiation and (re)myelination. T
reg
-deficient mice exhibited substantially impaired remyelination and oligodendrocyte differentiation, which was rescued by adoptive transfer of T
reg
. In brain slice cultures, T
reg
accelerated developmental myelination and remyelination, even in the absence of overt inflammation. T
reg
directly promoted oligodendrocyte progenitor cell differentiation and myelination
in vitro
. We identified CCN3 as a T
reg
-derived mediator of oligodendrocyte differentiation and myelination
in vitro
. These findings reveal a new regenerative function of T
reg
in the CNS, distinct from immunomodulation. Although the cells were originally named 'T
reg
' to reflect immunoregulatory roles, this also captures emerging, regenerative T
reg
functions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1097-6256 1546-1726 |
DOI: | 10.1038/nn.4528 |