多发性硬化
生物
主要组织相容性复合体
实验性自身免疫性脑脊髓炎
少突胶质细胞
免疫系统
背景(考古学)
谱系(遗传)
T细胞
谱系标记
抗原呈递
脱髓鞘病
髓鞘
免疫学
基因
神经科学
遗传学
中枢神经系统
表型
古生物学
作者
Ana Patrícia Siqueira Tavares Falcão,David van Bruggen,Sueli Marques,Mandy Meijer,Sarah Jäkel,Eneritz Agirre,Samudyata,Elisa Floriddia,Darya P. Vanichkina,Charles ffrench-Constant,Anna Williams,André Ortlieb Guerreiro-Cacais,Gonçalo Castelo-Branco
出处
期刊:Nature Medicine
[Springer Nature]
日期:2018-11-12
卷期号:24 (12): 1837-1844
被引量:289
标识
DOI:10.1038/s41591-018-0236-y
摘要
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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