Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA.
Mol Immunol. 2010 Apr;47(7-8):1595-600. doi: 10.1016/j.molimm.2010.02.001. Epub 2010 Mar 11.
Relative upregulation 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.
已有多个研究小组报道,Ikaros 家族转录因子 Helios 在天然调节性 T 细胞(Tregs)中呈相对上调表达。然而,Helios 在调节性 T 细胞中的作用尚未被描述。在这里,我们显示 Helios 在 CD4(+)CD25(+)调节性 T 细胞中呈上调表达。染色质免疫沉淀(ChIP)实验表明 Helios 结合到 FoxP3 启动子上。这些数据进一步通过实验得到证实,该实验表明用 siRNA 寡核苷酸敲低 Helios 会导致 FoxP3 的下调。功能上,我们发现 CD4(+)CD25(+)T 细胞中 Helios 信使的抑制显著减弱了其抑制功能。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 可能是一种在临床环境中操纵 Treg 活性的新靶标的概念。