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主题:NO在MSC介导的T细胞增殖抑制中发挥重要作用- B$ Y$ X8 o) X! g
9 D$ ^/ k3 w4 X2 N' n, B$ i说明:原文来自Blood,干细胞之家新闻小组成员deron翻译(转帖请注明)
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翻译内容:
8 a3 Z1 [- y4 P: W研究者对间充质干细胞抑制T细胞增殖的分子机制知之甚少,且一种可溶性因子是否发挥了一个主要作用仍有争议。本文我们证明了T细胞受体复合物并非抑制的作用靶点,间接证明下游信号介导了抑制作用。我们发现MSC存在时T细胞中Stat5磷酸化被抑制,且NO参与了Stat5磷酸化和T细胞增殖的抑制。MSC中容易检测到诱导型一氧化氮合酶(NOS)的表达,但T细胞中不易检测到,且一种特异性NOS抑制剂逆转了(NO)对Stat5磷酸化和T细胞增殖的抑制。在MSC存在的条件下,NO的产生由CD4 T细胞或CD8 T细胞而非由CD19 B细胞介导。此外,前列腺素合酶或NOS的抑制剂恢复了T细胞的增殖,但是IDO抑制剂和一种TGFβ中和抗体(对恢复T细胞增殖)无作用。最后,诱导型NOS缺陷小鼠来源MSC抑制T细胞增殖的能力下降。总体来说,这些结果表明MSC产生的NO是其抑制T细胞的主要介导物之一。7 t/ d( {+ c5 T5 }! Z1 K
原摘要:The molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell-receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor-beta-neutralizing antibody had no effect. Finally, MSCs from inducible NOS-/- mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.
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原文:
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文章说明:来自于2007年的Blood,研究主体为小鼠。 |
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