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Regulatory T cells promote myelin regeneration in the central nervous system

Accepted version
Peer-reviewed

Type

Article

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Authors

Dombrowski, Y 
O'Hagan, T 
Dittmer, M 
Penalva, R 
Mayoral, SR 

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.

Description

Keywords

lymphocytes, multiple sclerosis, neuroimmunology

Journal Title

Nature Neuroscience

Conference Name

Journal ISSN

1097-6256
1546-1726

Volume Title

20

Publisher

Nature Publishing Group
Sponsorship
Medical Research Council (MC_PC_12009)
Wellcome Trust (097922/Z/11/Z)
Multiple Sclerosis Society (50)
Multiple Sclerosis Society (941)
This work was supported by the Biotechnology and Biological Sciences Research Council (BB/J01026X/1 and BB/N003721/1, to D.C.F.), The Leverhulme Trust (ECF-2014-390, to Y.D.), QUB (QUB - Lucy McGuigan Bequest, to D.C.F.), The UK Multiple Sclerosis Society (941 and 50, to R.J.M.F. and C.Z.), MRC UK Regenerative Medicine platform (MR/KO26666/1, to A.C.W.), University of Edinburgh Wellcome Trust Multi User Equipment Grant (WT104915MA, to A.C.W.), by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute (097922/Z/11/Z to R.J.M.F.), studentship support from Dept. for the Economy (Northern Ireland) and British Pathological Society, US National Multiple Sclerosis Society (RG5203A4, to J.R.C.), NIH/NINDS (NS095889, to J.R.C.), NIH/NIGMS IRACDA Postdoctoral Fellowship (K12GM081266, to S.R.M.) and Wellcome Trust (110138/Z/15/Z, to D.C.F.).