A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells.
A role for the transcription factor Helios in human CD4(+)CD25(+) regulatory T cells.
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DOI：
10.1016/j.molimm.2010.02.001
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发表时间：
2010-04
影响因子：
3.6
通讯作者：
Drake CG
中科院分区：
文献类型：
--
作者：
Getnet D;Grosso JF;Goldberg MV;Harris TJ;Yen HR;Bruno TC;Durham NM;Hipkiss EL;Pyle KJ;Wada S;Pan F;Pardoll DM;Drake CG
Ikaros家族转录因子Helios在自然调节性T细胞（Tregs）中的相对上调已经被几个小组报道。然而，Helios在调节性T细胞中的作用尚未被描述。在这里，我们发现Helios在CD4+CD25+调节性T细胞中上调。染色质免疫沉淀（ChIP）实验表明Helios与FoxP3启动子结合。这些数据被实验进一步证实，用siRNA寡核苷酸敲除Helios导致FoxP3的下调。在功能上，我们发现在CD4+CD25+ T细胞中Helios信息的抑制显著减弱了它们的抑制功能。综上所述，这些数据表明Helios可能在调节性T细胞功能中发挥重要作用，并支持Helios可能是临床环境中操纵Treg活性的新靶点的概念。
Relative up-regulation of the Ikaros family transcription factor Helios in natural regulatory T cells (Tregs) has been reported by several groups. However, a role for Helios in regulatory T cells has not yet been described. Here, we show that Helios is upregulated in CD4+CD25+ regulatory T cells. Chromatin Immunoprecipitation (ChIP) experiments indicated that Helios binds to the FoxP3 promoter. These data were further corroborated by experiments showing that knocking-down Helios with siRNA oligonucleotides results in down-regulation of FoxP3. Functionally, we found that suppression of Helios message in CD4+CD25+ T cells significantly attenuates their suppressive function. Taken together, these data suggest that Helios may play an important role in regulatory T cell function and support the concept that Helios may be a novel target to manipulate Treg activity in a clinical setting.
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