Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, 225 South Chongqing Road, Shanghai 200025, China.
J Biol Chem. 2013 Apr 19;288(16):11074-9. doi: 10.1074/jbc.M112.414862. Epub 2013 Feb 28.
MSCs possess potent immunosuppressive capacity. We have reported that mouse MSCs inhibit T cell proliferation and function via nitric oxide. This immune regulatory capacity of MSCs is induced by the inflammatory cytokines IFNγ together with either TNFα or IL-1β. This effect of inflammatory cytokines on MSCs is extraordinary; logarithmic increases in the expression of iNOS and chemokines are often observed. To investigate the molecular mechanisms underlying this robust effect of cytokines, we examined the expression of microRNAs in MSCs before and after cytokine treatment. We found that miR-155 is most significantly up-regulated. Furthermore, our results showed that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression. We further demonstrated that miR-155 targets TAK1-binding protein 2 (TAB2) to regulate iNOS expression. Additionally, knockdown of TAB2 reduced iNOS expression. In summary, our study demonstrated that miR-155 inhibits the immunosuppressive capacity of MSCs by reducing iNOS expression by targeting TAB2. Our data revealed a novel role of miR-155 in regulating the immune modulatory activities of MSCs.
间充质干细胞（MSCs）具有强大的免疫抑制能力。我们曾报道过，鼠源 MSCs 通过一氧化氮（NO）抑制 T 细胞的增殖和功能。MSCs 的这种免疫调节能力是由炎症细胞因子 IFNγ 与 TNFα 或 IL-1β 共同诱导产生的。炎症细胞因子对 MSCs 的这种作用非常显著，通常会观察到 iNOS 和趋化因子的表达呈对数增加。为了研究细胞因子这种强大作用的分子机制，我们在细胞因子处理前后检测了 MSCs 中的 microRNA 表达。结果发现 miR-155 的表达上调最为显著。此外，我们的结果表明，miR-155 通过降低 iNOS 的表达来抑制 MSCs 的免疫抑制能力。我们进一步证明，miR-155 通过靶向 TAK1 结合蛋白 2（TAB2）来调节 iNOS 的表达。此外，TAB2 的敲低也降低了 iNOS 的表达。综上所述，我们的研究表明，miR-155 通过靶向 TAB2 降低 iNOS 的表达，从而抑制 MSCs 的免疫抑制能力。我们的数据揭示了 miR-155 在调节 MSCs 免疫调节活性方面的新作用。
