Astragalus polysaccharides promote neural stem cells-derived oligodendrogenesis through attenuating CD8+T cell infiltration in experimental autoimmune encephalomyelitis
Astragalus polysaccharides promote neural stem cells-derived oligodendrogenesis through attenuating CD8+T cell infiltration in experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.intimp.2023.111303
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发表时间：
2023-12-04
影响因子：
5.6
通讯作者：
Cheng，Xiaodong
中科院分区：
文献类型：
--
作者：
Zhao，Yan;Ma，Jinyun;Cheng，Xiaodong
内源性神经干细胞（NSCs）具有生成髓鞘再生少突胶质细胞的潜力，在多发性硬化症（MS）中发挥重要作用。然而，NSCs向少突胶质细胞的分化不足，这被认为是髓鞘再生失败的主要原因。我们之前的工作报道了黄芪多糖（APS）对实验性自身免疫性脑脊髓炎（EAE）小鼠具有神经保护作用。然而，APS是否调节EAE小鼠的NSCs分化尚不清楚。在本研究中，我们的数据表明，APS可以促进脑室下区（SVZ）的NSCs向少突胶质细胞分化。此外，我们发现黄芪多糖显著改善EAE小鼠的神经炎症，抑制CD8+T细胞向SVZ的浸润。我们还发现mog35 -55特异性CD8+T细胞通过分泌IFN-γ抑制NSCs向少突胶质细胞的分化，而APS促进NSCs向少突胶质细胞的分化与减少IFN-γ分泌有关。此外，APS处理对CD8+T细胞耗竭后的nsscs来源的少突胶质细胞形成没有更好的影响。本研究表明，APS可减轻神经炎症和CD8+T细胞浸润到SVZ，诱导少突胶质细胞分化，从而发挥神经保护作用。我们的研究结果表明，减少CD8+T细胞的浸润可能有助于增强nscs来源的神经发生。APS可能是一种很有前途的治疗多发性硬化症的候选药物。
Endogenous neural stem cells (NSCs) have the potential to generate remyelinating oligodendrocytes, which play an important role in multiple sclerosis (MS). However, the differentiation of NSCs into oligodendrocytes is insufficient, which is considered a major cause of remyelination failure. Our previous work reported thatAstragalus polysaccharides(APS) had a neuroprotective effect on experimental autoimmune encephalomyelitis (EAE) mice. However, it remains unclear whether APS regulate NSCs differentiation in EAE mice. In this study, our data illustrated that APS administration could promote NSCs in the subventricular zone (SVZ) to differentiate into oligodendrocytes. Furthermore, we found that APS significantly improved neuroinflammation and inhibited CD8+T cell infiltration into SVZ of EAE mice. We also found that MOG35-55-specific CD8+T cells suppressed NSCs differentiation into oligodendrocytes by secreting IFN-γ, and APS facilitated the differentiation of NSCs into oligodendrocytes which was related to decreased IFN-γ secretion. In addition, APS treatment did not show a better effect on the NSCs-derived oligodendrogenesis after CD8+T cell depletion. This present study demonstrated that APS alleviated neuroinflammation and CD8+T cell infiltration into SVZ to induce oligodendroglial differentiation, and thus exerted neuroprotective effect. Our findings revealed that reducing the infiltration of CD8+T cells might contribute to enhancing NSCs-derived neurogenesis. And APS might be a promising drug candidate to treat MS.