Noc4L-Mediated Ribosome Biogenesis Controls Activation of Regulatory and Conventional T Cells
Noc4L-Mediated Ribosome Biogenesis Controls Activation of Regulatory and Conventional T Cells
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Noc4L 介导的核糖体生物发生控制调节性 T 细胞和常规 T 细胞的激活
DOI：
10.1016/j.celrep.2019.03.083
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发表时间：
2019-04-23
期刊：
影响因子：
8.8
通讯作者：
Zhou, Xuyu
中科院分区：
文献类型：
--
作者：
Zhu, Xueping;Zhang, Wei;Zhou, Xuyu
调节性T细胞（Treg）活化对于维持自身耐受性至关重要，但这一过程的翻译调控仍然知之甚少。尽管核糖体生物合成被认为是一个管家过程，但新出现的证据支持这样的假设：核糖体生物合成可以通过调节翻译来选择性地调节蛋白质合成。在这里，我们专注于核糖体生物合成因子Noc4L，基于Noc4L在活化的TcB中高度表达的观察。条件Noc4L敲除导致一个致命的自身免疫表型类似Treg缺陷皮屑小鼠。有趣的是，Noc4L缺陷并没有全面影响TcG中的整体蛋白质翻译，但选择性地不利于与Treg激活相关的mRNA的表达。这些结果证明了Noc 4L介导的核糖体生物合成在控制Tcl3的活化和维持免疫耐受中的关键作用。
Regulatory T cell (Treg) activation is crucial for maintaining self-tolerance, but the translational regulation of this process is still poorly understood. Although ribosome biogenesis is considered a housekeeping process, emerging evidence supports the hypothesis that ribosome biogenesis can selectively regulate protein synthesis by tuning translation. Here, we focused on the ribosome biogenesis factor Noc4L, based on the observations that Noc4L is highly expressed in activated Tregs. Conditional Noc4L knockout in Tregs resulted in a lethal autoimmune phenotype resembling Treg-deficient scurfy mice. Interestingly, the Noc4L defect did not globally affect overall protein translation in Tregs but was selectively detrimental to the expression of mRNAs related to Treg activation. These results demonstrate the critical role of Noc4L-mediated ribosome biogenesis in controlling the activation of Tregs and maintaining immune tolerance.