A role for the transcription factor Helios in human CD4+CD25+ regulatory T cells

被引:177
作者
Getnet, Derese [1 ]
Grosso, Joseph F. [1 ]
Goldberg, Monica V. [1 ]
Harris, Timothy J. [1 ]
Yen, Hung-Rong [1 ,2 ]
Bruno, Tullia C. [1 ]
Durham, Nicholas M. [1 ]
Hipkiss, Edward L. [1 ]
Pyle, Kristin J. [1 ]
Wada, Satoshi [1 ]
Pan, Fan [1 ]
Pardoll, Drew M. [1 ]
Drake, Charles G. [1 ,3 ]
机构
[1] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA
[2] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Tao Yuan 333, Taiwan
[3] Johns Hopkins Univ, James Buchanan Brady Urol Inst, Baltimore, MD USA
基金
美国国家卫生研究院;
关键词
Regulatory T cells; Helios; FoxP3; FACTOR FOXP3; TGF-BETA; EXPRESSION; IKAROS;
D O I
10.1016/j.molimm.2010.02.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1595 / 1600
页数:6
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