1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences , School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, People's Republic of China .
2 Central Laboratory, Liaocheng People's Hospital , Liaocheng, People's Republic of China .
Stem Cells Dev. 2018 Apr 15;27(8):556-565. doi: 10.1089/scd.2017.0235.
Mesenchymal stem cells (MSCs) have a superior immunomodulatory capacity compared to other cells of the immune system, and they hold great promise for treating various immune disorders. However, their regulatory effects on the maturation of immature dendritic cells (imDCs) are not fully understood. In this study, we show that Sca-1LinCD117MSCs restrain the lipopolysaccharide-stimulated maturation transition of imDCs cocultured without exogenous cytokines. The Notch signaling pathway plays a critical role in the process by controlling interferon regulatory factor 8 (IRF8) expression in an RBP-J-dependent manner. We observed a high degree of H3K27me3 modification mediated by SUZ12 and a relatively low degree of H3K4me3 modification regulated by WDR5 at the IRF8 promoter during coculture. These data reveal a possible mechanism by which Sca-1LinCD117MSCs modulate imDC maturation and further support the role of MSCs in treating immune disorders.
间充质干细胞 (MSCs) 具有比免疫系统其他细胞更强的免疫调节能力，它们在治疗各种免疫紊乱方面具有很大的潜力。然而，它们对未成熟树突状细胞 (imDCs) 成熟的调节作用尚不完全清楚。在这项研究中，我们表明 Sca-1LinCD117MSCs 抑制无外源性细胞因子共培养的 LPS 刺激的 imDCs 成熟过渡。Notch 信号通路通过依赖于 RBP-J 的方式控制干扰素调节因子 8 (IRF8) 的表达，在该过程中发挥关键作用。我们观察到在共培养过程中，IRF8 启动子处存在高度的 H3K27me3 修饰，由 SUZ12 介导，以及相对较低的 H3K4me3 修饰，由 WDR5 调节。这些数据揭示了 Sca-1LinCD117MSCs 调节 imDC 成熟的可能机制，并进一步支持了 MSCs 在治疗免疫紊乱中的作用。
