Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells
Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells
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DOI：
10.1038/ni.1884
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发表时间：
2010-07-01
影响因子：
30.5
通讯作者：
Li, Ming O.
中科院分区：
文献类型：
--
作者：
Ouyang, Weiming;Beckett, Omar;Li, Ming O.
以表达转录因子Foxp3为特征的CD4（+）调节性T细胞（T-reg细胞）在维持免疫耐受中起着关键作用。在这里，我们发现Foxo1和Foxo3转录因子（在这里统称为“Foxo蛋白”）T细胞特异性缺失的小鼠发展为致命的多灶性炎症性疾病，部分原因是T-reg细胞缺陷。Foxo蛋白以T-reg细胞固有的方式调节胸腺和转化生长因子- β (tgf - β)诱导的Foxp3表达，这与Foxo蛋白结合Foxp3位点和控制Foxp3启动子活性的能力一致。转录组分析表明，Foxo蛋白调节其他T-reg细胞相关基因的表达，并且是抑制T-reg细胞获得效应T细胞特征所必需的。因此，Foxo蛋白在指定T-reg细胞谱系中起着至关重要的作用。
CD4(+) regulatory T cells (T-reg cells) characterized by expression of the transcription factor Foxp3 have a pivotal role in maintaining immunological tolerance. Here we show that mice with T cell-specific deletion of both the Foxo1 and Foxo3 transcription factors (collectively called 'Foxo proteins' here) developed a fatal multifocal inflammatory disorder due in part to T-reg cell defects. Foxo proteins functioned in a T-reg cell-intrinsic manner to regulate thymic and transforming growth factor-beta (TGF-beta)-induced Foxp3 expression, in line with the ability of Foxo proteins to bind to Foxp3 locus and control Foxp3 promoter activity. Transcriptome analyses showed that Foxo proteins regulated the expression of additional T-reg cell-associated genes and were essential for inhibiting the acquisition of effector T cell characteristics by T-reg cells. Thus, Foxo proteins have crucial roles in specifying the T-reg cell lineage.