Upregulation of chemokine receptor expression by IL-10/IL-4 in adult neural stem cells
Upregulation of chemokine receptor expression by IL-10/IL-4 in adult neural stem cells
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DOI：
10.1016/j.yexmp.2008.07.003
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发表时间：
2008-12-01
影响因子：
3.6
通讯作者：
Zhang, Guang-Xian
中科院分区：
文献类型：
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作者：
Guan, Yangtai;Jiang, Zhilong;Zhang, Guang-Xian
已经显示过继转移的成体神经干细胞（NSC）通过分化为髓鞘形成细胞来改善实验性自身免疫性脑脊髓炎（EAE）。然而，NSC迁移到病变病灶中是低效且相对缓慢的，导致仅适度的治疗效果。NSC迁移效率低下的一个可能原因可能是这些细胞产生抗炎细胞因子，这可能反过来抑制它们的迁移。为了解决这个问题，我们建立了室管膜下区来源的NSC神经球，并确定了IL-10和IL-4对这些细胞表达趋化因子受体的影响，以及对EAE发病机制相关趋化因子的迁移反应的影响。我们发现用IL-4和IL-10处理可上调NSC上的表面粘附分子LFA-1和趋化因子受体CXCR 4和CCR 5。IL-10处理的神经干细胞表现出显着更高的趋化性，上述趋化因子受体的配体比未处理的细胞。用IL-4处理NSC也导致这些细胞对RANTES的更高的趋化性。因此，在体外预处理与细胞因子可能是一个有用的方法，以促进迁移的神经干细胞进入中枢神经系统炎症灶，产生更强的治疗效果。这种方法有可能改善神经系统疾病（如多发性硬化症）的神经干细胞治疗的临床结果。(C)2008年爱思唯尔公司All rights reserved.
It has been shown that adoptively transferred adult neural stem cells (NSCs) ameliorate experimental autoimmune encephalomyelitis (EAE) by differentiating into myelin-forming cells. However, NSC migration into the lesion foci is inefficient and relatively slow, resulting in only modest therapeutic effect. A possible reason for the inefficient migration of NSCs could be the production of anti-inflammatory cytokines by these cells, which might in turn suppress their migration. To address this question we established subventricular zone-derived NSC neurospheres and determined the influence of IL-10 and IL-4 on chemokine receptor expression by these cells, and on their migration in response to chemokines relevant to EAE pathogenesis. We found that treatment with IL-4 and IL-10 upregulates surface adhesion molecule LFA-1 and chemokine receptors CXCR4 and CCR5 on NSCs. IL-10-treated NSCs exhibited significantly higher chemotaxis to the ligands of the above chemokine receptors than untreated cells. Treatment of NSC with IL-4 also resulted in a higher chemotaxis of these cells to RANTES. Thus, in vitro pretreatment with cytokines may be a useful approach to facilitate migration of NSCs into CNS inflammatory foci, producing stronger therapeutic effects. This approach has the potential to improve clinical outcomes of NSC-based therapies for neurological disorders such as multiple sclerosis. (C) 2008 Elsevier Inc. All rights reserved.