神经退行性变
实验性自身免疫性脑脊髓炎
髓鞘少突胶质细胞糖蛋白
多发性硬化
神经科学
神经炎症
视神经脊髓炎
生物
免疫学
医学
作者
Shihori Tanabe,Toshio Yamashita
出处
期刊:Cell Reports
[Elsevier]
日期:2014-11-01
卷期号:9 (4): 1459-1470
被引量:36
标识
DOI:10.1016/j.celrep.2014.10.038
摘要
Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, demyelination, and neurodegeneration in the CNS. Although it is important to prevent neurodegeneration for alleviating neurological disability, the molecular mechanism of neurodegeneration remains largely unknown. Here, we report that repulsive guidance molecule-a (RGMa), known to regulate axonal growth, is associated with neurodegeneration in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. RGMa is highly expressed in interleukin-17-producing CD4(+) T cells (Th17 cells). We induced EAE by adoptive transfer of myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells and then inhibited RGMa with a neutralizing antibody. Inhibition of RGMa improves EAE scores and reduces neuronal degeneration without altering immune or glial responses. Th17 cells induce cultured cortical neuron death through RGMa-neogenin and Akt dephosphorylation. Our results demonstrate that RGMa is involved in Th17-cell-mediated neurodegeneration and that RGMa-specific antibody may have a therapeutic effect in MS.
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