Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature
Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature
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DOI：
10.1016/j.immuni.2007.09.010
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发表时间：
2007-11-01
期刊：
影响因子：
32.4
通讯作者：
Benoist, Christophe
中科院分区：
文献类型：
--
作者：
Hill, Jonathan A.;Feuerer, Markus;Benoist, Christophe
调节性T（Treg）细胞的CD4(+)CD25(+)谱系在控制免疫和自身免疫应答中起关键作用，并具有独特的转录特征。转录因子Foxp3曾被认为决定了Treg细胞谱系，但这一假说受到近期观察结果的挑战。我们对在多种有或无Foxp3的条件下产生的类Treg细胞的Treg细胞特征进行了横断面分析，以描绘可归因于T细胞活化、白细胞介素 - 2、转化生长因子 - β（TGF - β）信号传导或Foxp3自身的要素。这些影响协同作用，决定了该特征的许多组成部分。Treg细胞的大部分特征不能归因于Foxp3，因为它包含与Foxp3共同调节但不由其反式激活的基因簇。因此，Foxp3上游更高级别的调控决定了谱系，这不同于对其调节特性至关重要的Foxp3下游要素。
The CD4(+)CD25(+) lineage of regulatory T (Treg) cells plays a key role in controlling immune and autoimmune responses and is characterized by a unique transcriptional signature. The transcription factor Foxp3 had been thought to determine the Treg cell lineage, a hypothesis challenged by recent observations. We have performed a cross-sectional analysis of the Treg cell signature in Treg-like cells generated under a number of conditions, with or without Foxp3, to delineate the elements that can be ascribed to T cell activation, interleukin-2, transforming growth factor-beta (TGF-beta) signaling, or Foxp3 itself. These influences synergized to determine many of the signature's components. Much of the Treg cell signature was not ascribable to Foxp3 because it contained gene clusters that are coregulated with, but not transactivated by, Foxp3. Thus, a higher level of regulation upstream of Foxp3 determines the lineage, distinct from elements downstream of Foxp3 that are essential for its regulatory properties.