Ubiquitin-dependent regulation of Foxp3 and Treg function.
Ubiquitin-dependent regulation of Foxp3 and Treg function.
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DOI：
10.1111/imr.12312
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发表时间：
2015-07
影响因子：
8.7
通讯作者：
Pan F
中科院分区：
文献类型：
--
作者：
Barbi J;Pardoll DM;Pan F
调节性T（Treg）细胞是免疫稳态的重要执行者。它们特有的抑制功能很大程度上源于同样独特的基因表达模式。一个复杂的因子和过程网络促成了这种“签名”Treg基因表达景观。其中许多改变Treg定义转录因子Foxp3的水平和活性。由于Foxp3的稳定表达对于Treg细胞成功防止过度或不适当的免疫激活的能力是重要的，因此需要揭示调节Foxp3水平的机制以理解和治疗开发Treg。虽然已经深入研究了Foxp3基因的转录调控，但存在控制该关键转录因子的表达和活性的另外的调控层。这些包括在翻译后水平上活跃的不太明确的机制。这些途径才刚刚开始被阐明。在这里，我们总结了新出现的证据，不同的，postperformancially活跃的，泛素依赖的途径能够控制Foxp3的激活和表达和功能的Tclase。这些途径提供了未开发的机会，用于治疗性微调TcB及其对免疫系统的所有重要抑制。
Regulatory T (Treg) cells are crucial enforcers of immune homeostasis. Their characteristic suppressive function largely arises from an equally unique pattern of gene expression. A complex network of factors and processes contribute to this ‘signature’ Treg gene expression landscape. Many of these alter the level and activity of the Treg-defining transcription factor Foxp3. Since stable expression of Foxp3 is important for the ability of Treg cells to successfully prevent excessive or inappropriate immune activation, uncovering the mechanisms regulating Foxp3 level is required for the understanding and therapeutic exploitation of Tregs. While transcriptional regulation of the Foxp3 gene has been studied in depth, additional regulatory layers exist controlling the expression and activity of this key transcription factor. These include less-defined mechanisms active at the posttranslational level. These pathways are just beginning to be elucidated. Here we summarize emerging evidence for distinct, posttranslationally active, ubiquitin-dependent pathways capable of controlling the activation and expression of Foxp3 and the function of Tregs. These pathways offer untapped opportunities for therapeutic fine-tuning of Tregs and their all-important restraint of the immune system.