Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis

Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41591-018-0236-y
Journal or Publication Title: Nature Medicine
Volume: 24
Number: 12
Page Range: pp. 1837-1844
Date: 2018
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.1038/s41591-018-0236-y
ISSN: 1078-8956
Date Deposited: 03 Jan 2021 23:29
Abstract:

Multiple sclerosis (MS) is characterized by an immune system attack targeting myelin, which is produced by oligodendrocytes (OLs). We performed single-cell transcriptomic analysis of OL lineage cells from the spinal cord of mice induced with experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of MS. We found unique OLs and OL precursor cells (OPCs) in EAE and uncovered several genes specifically alternatively spliced in these cells. Surprisingly, EAE-specific OL lineage populations expressed genes involved in antigen processing and presentation via major histocompatibility complex class I and II (MHC-I and -II), and in immunoprotection, suggesting alternative functions of these cells in a disease context. Importantly, we found that disease-specific oligodendroglia are also present in human MS brains and that a substantial number of genes known to be susceptibility genes for MS, so far mainly associated with immune cells, are expressed in the OL lineage cells. Finally, we demonstrate that OPCs can phagocytose and that MHC-II-expressing OPCs can activate memory and effector CD4-positive T cells. Our results suggest that OLs and OPCs are not passive targets but instead active immunomodulators in MS. The disease-specific OL lineage cells, for which we identify several biomarkers, may represent novel direct targets for immunomodulatory therapeutic approaches in MS.

Conflict of interest statement
Competing interests:

The G.C-B research group has received funding from F. Hoffmann – La Roche, Ltd. for another research project in the area.

Creators:
Creators
Email
Falcão, Ana Mendanha
UNSPECIFIED
van Bruggen, David
UNSPECIFIED
Marques, Sueli
UNSPECIFIED
Meijer, Mandy
UNSPECIFIED
Jäkel, Sarah
UNSPECIFIED
Agirre, Eneritz
UNSPECIFIED
Samudyata
UNSPECIFIED
Floriddia, Elisa M.
UNSPECIFIED
Vanichkina, Darya P.
UNSPECIFIED
ffrench-Constant, Charles
UNSPECIFIED
Williams, Anna
UNSPECIFIED
Guerreiro-Cacais, André Ortlieb
UNSPECIFIED
Castelo-Branco, Gonçalo
UNSPECIFIED
Last Modified: 03 Jan 2021 23:29
URI: https://eprints.centenary.org.au/id/eprint/526

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