Silencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis.

Silencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis.
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沉默 miR-150 可改善实验性自身免疫性脑脊髓炎

DOI:
10.3389/fnins.2018.00465
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发表时间:
2018
影响因子:
4.3
通讯作者:
Dai R
Dai R
中科院分区:
医学2区
文献类型:
--
作者:
Hu Z;Cui Y;Qiao X;He X;Li F;Luo C;Wang S;Li C;Dai R

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miR-150调节T细胞的成熟和分化,但它在多发性硬化症(MS)中的作用尚不清楚。在miR-150敲除(KO)小鼠中,我们检查了miR-150缺失对实验性自身免疫性脑脊髓炎(EAE)(MS的动物模型)疾病严重程度的影响。组织学染色和MBP免疫荧光染色显示miR-150缺失限制了脊髓中炎性脱髓鞘和轴突损伤的程度。流式细胞术显示,WT-EAE小鼠中CD 3+、CD 4+和CD 8 + T细胞增加,但miR-150缺失显著逆转了EAE介导的CD 3+、CD 4+和CD 8 + T细胞上调以及CD 19 + B细胞下调。此外,miR-150缺失降低了EAE诱导后脾脏和脊髓中IL-1β、IL-6、IL-17和TNF-α的mRNA表达。因此,miR-150缺失可能通过抑制中枢神经系统中激活的免疫应答和炎症来降低EAE的严重程度和脱髓鞘。
MiR-150 regulates maturation and differentiation of T cells but how it functions in multiple sclerosis (MS) is unclear. In miR-150 knockout (KO) mice, we examined the effect of miR-150 deletion on disease severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. After deleting miR-150, EAE disease severity was reduced according to clinical score. Histological staining and MBP immunofluorescence staining revealed that miR-150 deletion limited the extent of inflammatory demyelination and axonal damage in the spinal cord. Flow cytometry showed that CD3+, CD4+, and CD8+ T cells were increased in WT-EAE mice, but miR-150 deletion significantly reversed EAE-mediated up-regulation of CD3+, CD4+, and CD8+ T cells and down-regulation of CD19+ B cells. In addition, miR-150 deletion reduced the mRNA expression of IL-1β, IL-6, IL-17, and TNF-α in spleen and spinal cord after EAE induction. Thus, miR-150 deletion reduces EAE severity and demyelination, probably through inhibiting the activated immune response and the inflammation in the central nervous system.
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