期刊
NATURE MEDICINE
卷 24, 期 12, 页码 1837-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-018-0236-y
关键词
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资金
- University of Sydney HPC Grand Challenge Award
- Boehringer Ingelheim Travel Grant
- UK Multiple Sclerosis Society
- European Union, Horizon 2020, Marie-Sklodowska Curie Actions [EC 789492, SOLO 794689]
- European Committee for Treatment and Research of Multiple Sclerosis (ECTRIMS)
- Swedish Research Council [2015-03558]
- European Union (Horizon 2020 Research and Innovation Programme/European Research Council Consolidator Grant EPIScOPE) [681893]
- Swedish Brain Foundation [FO2017-0075]
- Ming Wai Lau Centre for Reparative Medicine
- Petrus och Augusta Hedlunds Foundation [M-2014-0041, M-2016-0428]
- Karolinska Institutet
- Wellcome Trust Investigator award
- MRC [MR/L016400/1, MR/P016022/1, MR/K026666/1] Funding Source: UKRI
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.
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