title: Regulatory T cells promote myelin regeneration in the central nervous system.
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, Tregaccelerated developmental myelination and remyelination, even in the absence of overt inflammation. Tregdirectly 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 Tregin the CNS, distinct from immunomodulation. Although the cells were originally named 'Treg' to reflect immunoregulatory roles, this also captures emerging, regenerative Tregfunctions.
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: O'Hagan
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Dittmer
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Rosana
authors.initials: R
authors.lastname: Penalva
authors.affiliation: Department of Neurology and Program in Neurosciences, University of California, San Francisco, California, USA.
authors.forename: Sonia R
authors.initials: SR
authors.lastname: Mayoral
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Bankhead
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Samara
authors.initials: S
authors.lastname: Fleville
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: George
authors.initials: G
authors.lastname: Eleftheriadis
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, UK.
authors.forename: Chao
authors.identifier: http://orcid.org/0000-0003-1144-1621
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Naughton
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Moffat
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: John
authors.initials: J
authors.lastname: Falconer
authors.affiliation: Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Boyd
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Hamilton
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Ingrid V
authors.initials: IV
authors.lastname: Allen
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.|Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Ireland.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Moynagh
authors.affiliation: Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Evergren
authors.affiliation: Université Côte d'Azur, CNRS, GREDEG, Nice, France.|International CCN Society, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Perbal
authors.affiliation: Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK.
authors.forename: Anna C
authors.identifier: http://orcid.org/0000-0002-6329-382X
authors.initials: AC
authors.lastname: Williams
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ingram
authors.affiliation: Department of Neurology and Program in Neurosciences, University of California, San Francisco, California, USA.
authors.forename: Jonah R
authors.initials: JR
authors.lastname: Chan
authors.affiliation: Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, Clifford Allbutt Building, Cambridge Biomedical Campus, University of Cambridge, UK.
authors.forename: Robin J M
authors.initials: RJM
authors.lastname: Franklin
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen's University Belfast, Northern Ireland, UK.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology* / Q000648:ultrastructure; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000502:physiology*; D055514:Nephroblastoma Overexpressed Protein / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: C526320:Ccn3 protein, mouse; D055514:Nephroblastoma Overexpressed Protein