Regulatory T cells promote myelin regeneration in the central nervous system

被引：360

作者：

Dombrowski, Yvonne ^{[1
]}

O'Hagan, Thomas ^{[1
]}

Dittmer, Marie ^{[1
]}

Penalva, Rosana ^{[1
]}

Mayoral, Sonia R. ^{[2
,3
]}

Bankhead, Peter ^{[4
]}

Fleville, Samara ^{[1
]}

Eleftheriadis, George ^{[1
]}

Zhao, Chao ^{[5
]}

Naughton, Michelle ^{[1
]}

Hassan, Rachel ^{[1
]}

Moffat, Jill ^{[1
]}

Falconer, John ^{[1
]}

Boyd, Amanda ^{[6
]}

Hamilton, Peter ^{[4
]}

Allen, Ingrid V. ^{[1
]}

Kissenpfennig, Adrien ^{[1
]}

Moynagh, Paul N. ^{[1
,7
]}

Evergren, Emma ^{[4
]}

Perbal, Bernard ^{[8
,9
]}

Williams, Anna C. ^{[6
]}

Ingram, Rebecca J. ^{[1
]}

Chan, Jonah R.

Franklin, Robin J. M. ^{[5
]}

Fitzgerald, Denise C. ^{[1
]}

机构：

[1] Queens Univ Belfast, Ctr Expt Med, Sch Med Dent & Biomed Sci, Belfast, North Ireland

[2] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Program Neurosci, San Francisco, CA 94143 USA

[4] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, Belfast, North Ireland

[5] Univ Cambridge, Cambridge Stem Cell Inst, Wellcome Trust Med Res Council, Clifford Allbutt Bldg,Cambridge Biomedical Campus, Cambridge, England

[6] Univ Edinburgh, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland

[7] Natl Univ Ireland Maynooth, Inst Immunol, Dept Biol, Maynooth, Kildare, Ireland

[8] Univ Cote Azur, CNRS, GREDEG, Nice, France

[9] Int CCN Soc, Paris, France

来源：

NATURE NEUROSCIENCE | 2017年 / 20卷 / 05期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

MOUSE SPINAL-CORD; CNS REMYELINATION; DIFFERENTIAL EXPRESSION; INDUCED DEMYELINATION; MULTIPLE-SCLEROSIS; CCN FAMILY; MICE; REPAIR; MACROPHAGES; ACTIVATION;

D O I：

10.1038/nn.4528

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：674 / +

页数：10

共 42 条

[1] bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS [J].