Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3.
Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3.
复制标题
DOI：
10.1016/j.celrep.2016.11.045
复制
发表时间：
2016-12
期刊：
影响因子：
8.8
通讯作者：
Katharina S. Rauch;Miriam Hils;Ekaterina Lupar;S. Minguet;M. Sigvardsson;M. Rottenberg;A. Izcue;C. S
中科院分区：
文献类型：
--
作者：
Katharina S. Rauch;Miriam Hils;Ekaterina Lupar;S. Minguet;M. Sigvardsson;M. Rottenberg;A. Izcue;C. S
转录因子Foxp 3主要控制调节性T（Treg）细胞功能，并且只有其持续表达才能保证维持完整的Treg细胞抑制能力。然而，转录调控因子foxp 3转录不完全描述。在这里，我们报告说，高E47转录因子在Treg细胞的活性导致不稳定的Foxp 3表达。在稳态条件下，Treg细胞表达高水平的E47拮抗剂Id 3，从而限制E47活性并维持Foxp 3表达。相反，Id 3缺陷或E47过表达Treg细胞的刺激导致体内和体外Treg细胞亚群中Foxp 3表达的丧失。机制分析表明，E47激活转录因子Spi-B和细胞因子信号转导抑制因子3（SOCS 3）的表达，这两者都下调Foxp 3的表达。这些发现表明Id 3和E47的平衡控制Treg细胞中Foxp 3表达的维持，因此有助于Treg细胞的可塑性。
The transcription factor Foxp3 dominantly controls regulatory T (Treg) cell function, and only its continuous expression guarantees the maintenance of full Treg cell-suppressive capacity. However, transcriptional regulators maintainingFoxp3transcription are incompletely described. Here, we report that high E47 transcription factor activity in Treg cells resulted in unstable Foxp3 expression. Under homeostatic conditions, Treg cells expressed high levels of the E47 antagonist Id3, thus restricting E47 activity and maintaining Foxp3 expression. In contrast, stimulation of Id3-deficient or E47-overexpressing Treg cells resulted in the loss of Foxp3 expression in a subset of Treg cells in vivo and in vitro. Mechanistic analysis indicated that E47 activated expression of the transcription factor Spi-B and the suppressor of cytokine signaling 3 (SOCS3), which both downregulated Foxp3 expression. These findings demonstrate that the balance of Id3 and E47 controls the maintenance of Foxp3 expression in Treg cells and, thus, contributes to Treg cell plasticity.