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
相关论文
共 28 条
  • [1] Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production
    Allan, Sarah E.
    Crome, Sarah Q.
    Crellin, Natasha K.
    Passerini, Laura
    Steiner, Theodore S.
    Bacchetta, Rosa
    Roncarolo, Maria G.
    Levings, Megan K.
    [J]. INTERNATIONAL IMMUNOLOGY, 2007, 19 (04) : 345 - 354
  • [2] Helios Deficiency Has Minimal Impact on T Cell Development and Function
    Cai, Qi
    Dierich, Andree
    Oulad-Abdelghani, Mustapha
    Chan, Susan
    Kastner, Philippe
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 183 (04) : 2303 - 2311
  • [3] Role of regulatory T cells in human diseases
    Chatila, TA
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 116 (05) : 949 - 959
  • [4] Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-β induction of transcription factor Foxp3
    Chen, WJ
    Jin, WW
    Hardegen, N
    Lei, KJ
    Li, L
    Marinos, N
    McGrady, G
    Wahl, SM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (12) : 1875 - 1886
  • [5] Regulatory T cells and intestinal homeostasis
    Coombes, JL
    Robinson, NJ
    Maloy, KJ
    Uhlig, HH
    Powrie, F
    [J]. IMMUNOLOGICAL REVIEWS, 2005, 204 : 184 - 194
  • [6] Regulatory T cells and treatment of cancer
    Curiel, Tyler J.
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2008, 20 (02) : 241 - 246
  • [7] Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor?
    de Lafaille, Maria A. Curotto
    Lafaille, Juan J.
    [J]. IMMUNITY, 2009, 30 (05) : 626 - 635
  • [8] Regulatory T cell lineage specification by the forkhead transcription factor FoxP3
    Fontenot, JD
    Rasmussen, JP
    Williams, LM
    Dooley, JL
    Farr, AG
    Rudensky, AY
    [J]. IMMUNITY, 2005, 22 (03) : 329 - 341
  • [9] Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells (Reprinted from vol 4, pg 330-336, 2003)
    Fontenot, Jason D.
    Gavin, Marc A.
    Rudensky, Alexander Y.
    [J]. JOURNAL OF IMMUNOLOGY, 2017, 198 (03) : 986 - 992
  • [10] Tumor Recognition and Self-Recognition Induce Distinct Transcriptional Profiles in Antigen-Specific CD4 T Cells
    Getnet, Derese
    Maris, Charles H.
    Hipkiss, Edward L.
    Grosso, Joseph F.
    Harris, Timothy J.
    Yen, Hung-Rong
    Bruno, Tullia C.
    Wada, Satoshi
    Adler, Adam
    Georgantas, Robert W.
    Jie, Chunfa
    Goldberg, Monica V.
    Pardoll, Drew M.
    Drake, Charles G.
    [J]. JOURNAL OF IMMUNOLOGY, 2009, 182 (08) : 4675 - 4685