Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells.
Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells.
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Foxp 3在调节性T（Treg）细胞建立稳定的转录和功能程序中起着不可或缺的作用。成熟Treg细胞中Foxp 3表达的缺失导致抑制功能的失败，但确保Treg细胞谱系中稳定的可遗传Foxp 3表达的分子机制仍然未知。使用Treg细胞特异性基因靶向，我们发现Runx-CBFβ复合物是维持Treg细胞中Foxp 3 mRNA和蛋白表达所必需的。因此，仅在Treg细胞谱系中缺乏CBFβB的小鼠表现出中度淋巴细胞增殖综合征。因此，Runx-CBFβ复合物维持高量Foxp 3的稳定表达，并作为Treg细胞谱系稳定性的重要决定因素。
Foxp3 plays an indispensable role in establishing stable transcriptional and functional programs of regulatory T (Treg) cells. Loss of Foxp3 expression in mature Treg cells results in a failure of suppressor function, yet the molecular mechanisms ensuring steady heritable Foxp3 expression in the Treg cell lineage remain unknown. Using Treg cell-specific gene targeting we found that Runx-CBFβ complexes were required for maintenance of Foxp3 mRNA and protein expression in Treg cells. Consequently, mice lacking CBFβb exclusively in the Treg cell lineage exhibited a moderate lymphproliferative syndrome. Thus, Runx-CBFβ complexes maintain stable expression of high amounts of Foxp3 and serve as an essential determinant of Treg cell lineage stability.
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