Mesenchymal stem cells: a double-edged sword in regulating immune responses.
Mesenchymal stem cells: a double-edged sword in regulating immune responses.
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DOI：
10.1038/cdd.2012.26
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发表时间：
2012-09
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
间充质干细胞（MSC）已成功地用于治疗动物模型和临床环境中的各种免疫疾病。我们以前的研究表明，MSC可以成为高度免疫抑制后的刺激炎性细胞因子，通过发挥协同作用的趋化因子和一氧化氮（NO）的效果。在这里，我们表明MSC也可以增强免疫反应。当促炎细胞因子不足以引起足够的NO产生时，就会发生这种免疫促进作用。当诱导型一氧化氮合酶（iNOS）的生产被抑制或基因消融，骨髓间充质干细胞强烈增强T细胞增殖在体外和迟发型超敏反应在体内。此外，iNOS−/− MSC显著抑制黑色素瘤生长。很可能在没有NO的情况下，趋化因子会起到促进免疫反应的作用。事实上，在CCR 5 −/− CXCR 3 −/−小鼠中，iNOS−/− MSC的免疫促进作用大大减弱。因此，NO在MSC介导的免疫调节中充当开关。更重要的是，在人MSC中也观察到对免疫反应的双重作用，其中吲哚胺2，3-双加氧酶（IDO）充当开关。这项研究提供了新的信息，骨髓间充质干细胞的病理生理作用。
Mesenchymal stem cells (MSCs) have been employed successfully to treat various immune disorders in animal models and clinical settings. Our previous studies have shown that MSCs can become highly immunosuppressive upon stimulation by inflammatory cytokines, an effect exerted through the concerted action of chemokines and nitric oxide (NO). Here, we show that MSCs can also enhance immune responses. This immune-promoting effect occurred when proinflammatory cytokines were inadequate to elicit sufficient NO production. When inducible nitric oxide synthase (iNOS) production was inhibited or genetically ablated, MSCs strongly enhance T-cell proliferation in vitro and the delayed-type hypersensitivity response in vivo. Furthermore, iNOS−/− MSCs significantly inhibited melanoma growth. It is likely that in the absence of NO, chemokines act to promote immune responses. Indeed, in CCR5−/−CXCR3−/− mice, the immune-promoting effect of iNOS−/− MSCs is greatly diminished. Thus, NO acts as a switch in MSC-mediated immunomodulation. More importantly, the dual effect on immune reactions was also observed in human MSCs, in which indoleamine 2,3-dioxygenase (IDO) acts as a switch. This study provides novel information about the pathophysiological roles of MSCs.
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影响因子：
20.3
作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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