ROG negatively regulates T-cell activation but is dispensable for Th-cell differentiation
ROG negatively regulates T-cell activation but is dispensable for Th-cell differentiation
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DOI：
10.1128/mcb.25.2.554-562.2005
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发表时间：
2005-01-01
影响因子：
5.3
通讯作者：
Ho, IC
中科院分区：
文献类型：
--
作者：
Kang, BY;Miaw, SC;Ho, IC
ROG是一种转录抑制因子，是NF-AT的直接靶基因，被认为是t细胞活化的负调节因子。此外，过表达ROG可抑制GATA-3的活性，提示ROG在Th细胞的分化和功能中发挥作用。尽管有这些观察结果，ROG的功能尚未通过功能丧失方法得到证实。在这里，我们报告了rog缺陷T细胞对抗cd3刺激过敏，并且由于NF-kappaB活性增强而产生更多的白细胞介素-2 （IL-2）。缺乏rog的树突状细胞也产生更多的IL-12p40，另一种NF-kappaB靶基因。然而，rog缺陷的Th细胞能够分化为Th1和Th2细胞，并且rog缺陷的小鼠在体内建立适当的Th免疫反应没有缺陷。因此，ROG对于Th细胞的分化和功能是必不可少的，但它是nf - at启动的NF-kappaB抑制的中介。它的作用机制和表达模式不同于其他负向调节T细胞活化的转录因子。
ROG, a transcriptional repressor, is a direct target gene of NF-AT and a putative negative regulator of T-cell activation. In addition, overexpression of ROG suppresses the activity of GATA-3, implying a role of ROG in the differentiation and function of Th cells. Despite these observations, the function of ROG has yet to be confirmed by loss-of-function approaches. Here we report that ROG-deficient T cells are hypersensitive to anti-CD3 stimulation and produce more interleukin-2 (IL-2) due to enhanced NF-kappaB activity. ROG-deficient dendritic cells also produce more IL-12p40, another NF-kappaB target gene. However, ROG-deficient Th cells are capable of differentiating into Th1 and Th2 cells, and ROG-deficient mice have no defect in mounting appropriate Th immune responses in vivo. Thus, ROG is dispensable for the differentiation and function of Th cells but serves as a mediator of NF-AT-initiated suppression of NF-kappaB. Its mechanism of action and its expression pattern are distinct from those of other transcription factors negatively regulating the activation of T cells.