Regulatory T cells promote myelin regeneration in the central nervous system

Yvonne Dombrowski; Thomas O'Hagan; Marie Dittmer; Rosana Penalva; Sonia R Mayoral; Peter Bankhead; Samara Fleville; Georgios Eleftheriadis; Chao Zhao; Michelle Naughton; Rachel Hassan; Jill Moffat; John Falconer; Amanda Boyd; Peter Hamilton; Ingrid V Allen; Adrien Kissenpfennig; Paul N Moynagh; Emma Evergren; Bernard Perbal; Anna C Williams; Rebecca J Ingram; Jonah R Chan; Robin J M Franklin; Denise C Fitzgerald

doi:10.1038/nn.4528

Regulatory T cells promote myelin regeneration in the central nervous system

Yvonne Dombrowski, Thomas O'Hagan, Marie Dittmer, Rosana Penalva, Sonia R Mayoral, Peter Bankhead, Samara Fleville, Georgios Eleftheriadis, Chao Zhao, Michelle Naughton, Rachel Hassan, Jill Moffat, John Falconer, Amanda Boyd, Peter Hamilton, Ingrid V Allen, Adrien Kissenpfennig, Paul N Moynagh, Emma Evergren, Bernard PerbalAnna C Williams, Rebecca J Ingram, Jonah R Chan, Robin J M Franklin, Denise C Fitzgerald

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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.

Original language	English
Pages (from-to)	674–680
Number of pages	7
Journal	Nature Neuroscience
Volume	20
Issue number	5
Early online date	13 Mar 2017
DOIs	https://doi.org/10.1038/nn.4528
Publication status	Published - May 2017

Bibliographical note

Author contribution: As the Principal Investigator I conceptualised, designed, secured funding, supervised, managed and oversaw the study in QUB and with collaborators in California, USA, Cambridge UK, Edinburgh UK, Maynooth, Ireland and Nice, France. I wrote the paper with the first author and input from all authors.

Keywords

Journal Article

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10.1038/nn.4528Licence: Unspecified

Regulatory T cells promote myelin regeneration in the central nervous system
© 2017 Nature Publishing Group This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 4.01 MBLicence: Unspecified
NN-A57539B Control Remyelination
Copyright 2017 Nature Publishing. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
Other version, 6.24 MBLicence: Unspecified
NN-A57539B Treg-enhanced Remyelination
Copyright 2017 Nature Publishing. This work is made available online in accordance with the publisher’s policies. Please refer to any applicable terms of use of the publisher.
Other version, 1.9 MBLicence: Unspecified

http://rdcu.be/p220 Licence: Other
http://europepmc.org/abstract/MED/28288125Licence: Unspecified

Investigating interplay between human regulatory T cells and oligodendrocyte lineage cells
Author: Eleftheriadis, G., Jul 2020
Supervisor: Chandran, S. (Supervisor), Fitzgerald, D. (Supervisor) & Margariti, A. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy

Yvonne Dombrowski
- y.dombrowskiqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Lecturer
- Wellcome Wolfson Institute for Experimental Medicine
Person: Academic
Denise Fitzgerald
- d.fitzgeraldqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Professor
- Wellcome Wolfson Institute for Experimental Medicine
Person: Academic

Cite this

Dombrowski, Y., O'Hagan, T., Dittmer, M., Penalva, R., Mayoral, S. R., Bankhead, P., Fleville, S., Eleftheriadis, G., Zhao, C., Naughton, M., Hassan, R., Moffat, J., Falconer, J., Boyd, A., Hamilton, P., Allen, I. V., Kissenpfennig, A., Moynagh, P. N., Evergren, E., ... Fitzgerald, D. C. (2017). Regulatory T cells promote myelin regeneration in the central nervous system. Nature Neuroscience, 20(5), 674–680. https://doi.org/10.1038/nn.4528

Dombrowski, Yvonne ; O'Hagan, Thomas ; Dittmer, Marie ; Penalva, Rosana ; Mayoral, Sonia R ; Bankhead, Peter ; Fleville, Samara ; Eleftheriadis, Georgios ; Zhao, Chao ; Naughton, Michelle ; Hassan, Rachel ; Moffat, Jill ; Falconer, John ; Boyd, Amanda ; Hamilton, Peter ; Allen, Ingrid V ; Kissenpfennig, Adrien ; Moynagh, Paul N ; Evergren, Emma ; Perbal, Bernard ; Williams, Anna C ; Ingram, Rebecca J ; Chan, Jonah R ; Franklin, Robin J M ; Fitzgerald, Denise C. / Regulatory T cells promote myelin regeneration in the central nervous system. In: Nature Neuroscience. 2017 ; Vol. 20, No. 5. pp. 674–680.

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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, 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.",

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note = "Author contribution: As the Principal Investigator I conceptualised, designed, secured funding, supervised, managed and oversaw the study in QUB and with collaborators in California, USA, Cambridge UK, Edinburgh UK, Maynooth, Ireland and Nice, France. I wrote the paper with the first author and input from all authors.",

year = "2017",

month = may,

doi = "10.1038/nn.4528",

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Dombrowski, Y, O'Hagan, T, Dittmer, M, Penalva, R, Mayoral, SR, Bankhead, P, Fleville, S, Eleftheriadis, G, Zhao, C, Naughton, M, Hassan, R, Moffat, J, Falconer, J, Boyd, A, Hamilton, P, Allen, IV, Kissenpfennig, A , Moynagh, PN , Evergren, E, Perbal, B, Williams, AC, Ingram, RJ, Chan, JR, Franklin, RJM & Fitzgerald, DC 2017, 'Regulatory T cells promote myelin regeneration in the central nervous system', Nature Neuroscience, vol. 20, no. 5, pp. 674–680. https://doi.org/10.1038/nn.4528

Regulatory T cells promote myelin regeneration in the central nervous system. / Dombrowski, Yvonne; O'Hagan, Thomas; Dittmer, Marie; Penalva, Rosana; Mayoral, Sonia R; Bankhead, Peter; Fleville, Samara; Eleftheriadis, Georgios; Zhao, Chao; Naughton, Michelle; Hassan, Rachel; Moffat, Jill; Falconer, John; Boyd, Amanda; Hamilton, Peter; Allen, Ingrid V; Kissenpfennig, Adrien ; Moynagh, Paul N ; Evergren, Emma; Perbal, Bernard; Williams, Anna C; Ingram, Rebecca J; Chan, Jonah R; Franklin, Robin J M; Fitzgerald, Denise C.

In: Nature Neuroscience, Vol. 20, No. 5, 05.2017, p. 674–680.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Regulatory T cells promote myelin regeneration in the central nervous system

AU - Dombrowski, Yvonne

AU - O'Hagan, Thomas

AU - Dittmer, Marie

AU - Penalva, Rosana

AU - Mayoral, Sonia R

AU - Bankhead, Peter

AU - Fleville, Samara

AU - Eleftheriadis, Georgios

AU - Zhao, Chao

AU - Naughton, Michelle

AU - Hassan, Rachel

AU - Moffat, Jill

AU - Falconer, John

AU - Boyd, Amanda

AU - Hamilton, Peter

AU - Allen, Ingrid V

AU - Kissenpfennig, Adrien

AU - Moynagh, Paul N

AU - Evergren, Emma

AU - Perbal, Bernard

AU - Williams, Anna C

AU - Ingram, Rebecca J

AU - Chan, Jonah R

AU - Franklin, Robin J M

AU - Fitzgerald, Denise C

N1 - Author contribution: As the Principal Investigator I conceptualised, designed, secured funding, supervised, managed and oversaw the study in QUB and with collaborators in California, USA, Cambridge UK, Edinburgh UK, Maynooth, Ireland and Nice, France. I wrote the paper with the first author and input from all authors.

PY - 2017/5

Y1 - 2017/5

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/nn.4528

DO - 10.1038/nn.4528

M3 - Article

C2 - 28288125

VL - 20

SP - 674

EP - 680

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 5

ER -

Regulatory T cells promote myelin regeneration in the central nervous system

Abstract

Bibliographical note

Keywords

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Student Theses

Investigating interplay between human regulatory T cells and oligodendrocyte lineage cells

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Yvonne Dombrowski

Denise Fitzgerald

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