首页> 外文期刊>Nature immunology >Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization
【24h】

Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization

机译:Notch-RBP-J信号调节转录因子IRF8促进炎症性巨噬细胞极化

获取原文
获取原文并翻译 | 示例
           

摘要

Emerging concepts suggest that the functional phenotype of macrophages is regulated by transcription factors that define alternative activation states. We found that RBP-J, the main nuclear transducer of signaling via Notch receptors, augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of classically activated M1 macrophages and thus of innate immune responses to Listeria monocytogenes. Notch-RBP-J signaling controlled expression of the transcription factor IRF8 that induced downstream M1 macrophage-associated genes. RBP-J promoted the synthesis of IRF8 protein by selectively augmenting kinase IRAK2-dependent signaling via TLR4 to the kinase MNK1 and downstream translation-initiation control through eIF4E. Our results define a signaling network in which signaling via Notch-RBP-J and TLRs is integrated at the level of synthesis of IRF8 protein and identify a mechanism by which heterologous signaling pathways can regulate the TLR-induced inflammatory polarization of macrophages.
机译:新兴的概念表明,巨噬细胞的功能表型受转录因子的调控,转录因子定义了替代的激活状态。我们发现RBP-J,通过Notch受体信号转导的主要核转导,增加了Toll样受体4(TLR4)诱导的经典激活的M1巨噬细胞关键介体的表达,从而增强了对单核细胞增生性李斯特菌的先天免疫应答。 Notch-RBP-J信号传导诱导下游M1巨噬细胞相关基因的转录因子IRF8的表达。 RBP-J通过选择性增强经由TLR4传递至激酶MNK1的依赖激酶IRAK2的信号传导以及通过eIF4E进行下游翻译起始控制,促进了IRF8蛋白的合成。我们的结果定义了一个信号网络,其中通过Notch-RBP-J和TLRs的信号在IRF8蛋白的合成水平上得以整合,并确定了异源信号通路可以调节TLR诱导的巨噬细胞炎性极化的机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号