MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
PLoS One. 2011 Apr 7;6(4):e18670. doi: 10.1371/journal.pone.0018670.
Expression of the lineage-specific DNA-binding factor Foxp3 controls the development and function of naturally occurring regulatory T cells. Foxp3 has been shown to interact with a multitude of transcriptional regulators including NFAT, NF-κB (p65), Runx1 and RORγt, as well as the histone modification enzymes TIP60, HDAC7 and HDAC9. The sum of these interactions is believed to cause the change in the transcriptional program of regulatory T cells. Here we show that Foxp3 directly or as part of a multimeric complex engages with the NF-κB component c-Rel. We demonstrate that the N-terminal region of Foxp3 is required for the binding of c-Rel, but not NFAT. Conversely, deletion of the forkhead domain causes a loss of interaction with NFAT, but not c-Rel. Our findings are of particular interest, as c-Rel is crucial for the induction of Foxp3 in regulatory T cells during thymic development, but has to be repressed in mature regulatory T cells to maintain their suppressive phenotype.
谱系特异性 DNA 结合因子 Foxp3 的表达控制着天然调节性 T 细胞的发育和功能。Foxp3 已被证明与多种转录调节剂相互作用，包括 NFAT、NF-κB（p65）、Runx1 和 RORγt，以及组蛋白修饰酶 TIP60、HDAC7 和 HDAC9。这些相互作用的总和被认为导致了调节性 T 细胞转录程序的改变。在这里，我们表明 Foxp3 直接或作为多聚体复合物的一部分与 NF-κB 成分 c-Rel 结合。我们证明 Foxp3 的 N 端区域对于 c-Rel 的结合是必需的，但不是 NFAT。相反，叉头结构域的缺失导致与 NFAT 的相互作用丧失，但与 c-Rel 的相互作用不受影响。我们的发现特别有趣，因为 c-Rel 对于胸腺发育过程中调节性 T 细胞中 Foxp3 的诱导至关重要，但在成熟的调节性 T 细胞中必须被抑制以维持其抑制表型。
