Regulatory T cells suppress CD4+ T cells through NFAT-dependent transcriptional mechanisms

被引:39
作者
Shin, Daniel S. [1 ]
Jordan, Ayana [1 ]
Basu, Samik [1 ]
Thomas, Rajan M. [2 ,3 ]
Bandyopadhyay, Sanmay [1 ]
de Zoeten, Edwin F. [2 ,3 ]
Wells, Andrew D. [2 ,3 ]
Macian, Fernando [1 ]
机构
[1] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA
[2] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA
[3] Childrens Hosp Philadelphia, Res Inst, Philadelphia, PA 19104 USA
基金
美国国家卫生研究院;
关键词
Ikaros; NFAT; regulatory T cell; GENE-TRANSCRIPTION; REPRESSOR ICER; ANTIGEN; 4; TOLERANCE; INDUCTION; INFLAMMATION; ACETYLATION; LYMPHOCYTES; EXPRESSION; FACILITATE;
D O I
10.15252/embr.201338233
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
Regulatory T cells (Tregs) control autoreactive T cells by inhibiting activation-induced proliferation and cytokine expression. The molecular mechanisms responsible for the inactivation of effector T cells by Tregs remain yet to be fully characterized. We report that T-helper cells stimulated in the presence of Tregs quickly activate NFAT1 and have increased NFAT1-dependent expression of the transcription repressor Ikaros. NFAT1 deficiency or dominant-negative Ikaros compromises Treg-mediated inhibition of T-helper cells in vitro and in vivo. Thus, our results place NFAT-dependent mechanisms as general regulators of T-cell tolerance and show that Treg-mediated suppression of T-helper cells results from the activation of NFAT-regulated gene expression.
引用
收藏
页码:991 / 999
页数:9
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