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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Distal-less homeobox transcription factors regulate development and maturation of natural killer cells
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Distal-less homeobox transcription factors regulate development and maturation of natural killer cells

机译：无远端同源盒转录因子调节自然杀伤细胞的发育和成熟

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Natural killer (NK) cells constitute a subpopulation of lymphocytes that develop from precursors in the bone marrow (BM), but the transcriptional regulation of their development and maturation is only beginning to be understood, in part due to their relatively rare abundance, especially of developmental subsets. Using a mouse model in which NK cells are arrested at an immature stage of development, and a gene expression profiling approach, we uncovered transient normal NK cell expression of a homeobox transcription factor (TF) family, called Distal-less (D/x), which had been primarily implicated in murine CNS, craniofacial, limb, and skin development. Our studies demonstrate that Dlx1, Dlx2, and Dlx3 are transiently expressed in immature Mac-1~_(lo) NK cells within the BM, with Dlx3 being the predominantly expressed member. These genes are expressed in a temporally regulated pattern with overlapping waves of expression, and they display functional redundancy. Expression is extinguished in fully mature splenic NK cells, and persistent expression of Dlx genes leads to functionally immature NK cells arrested at the Mac-1~(lo) stage. Whereas conventional splenic NK cells develop but are arrested at an immature stage, there appears to be a complete failure to develop CD127~+ thymic NK cells when Dlx genes are persistently expressed. We also observed that T and B cells fail to develop in the context of persistent Dlx1 expression. Thus, these studies indicate that Dlx TFs play a functional role in lymphocyte development.
机译：自然杀伤（NK）细胞构成了从骨髓（BM）的前体发育而来的淋巴细胞的亚群，但是其发育和成熟的转录调控才刚刚开始被理解，部分是由于它们的相对稀有，尤其是它们的丰度。发展子集。使用小鼠模型，其中NK细胞在发育的不成熟阶段被捕，并采用基因表达谱分析方法，我们发现了同源异形盒转录因子（TF）家族的短暂正常NK细胞表达，称为Distal-less（D / x） ，这主要与鼠中枢神经系统，颅面，肢体和皮肤发育有关。我们的研究表明，Dlx1，Dlx2和Dlx3在BM内未成熟的Mac-1_（lo）NK细胞中瞬时表达，其中Dlx3是主要表达的成员。这些基因以时间调控的方式与重叠的表达波一起表达，并且显示出功能冗余。在完全成熟的脾脏NK细胞中表达消失，而Dlx基因的持续表达导致功能不成熟的NK细胞停滞在Mac-1〜（lo）阶段。常规的脾脏NK细胞会发育，但会在不成熟的阶段停滞，而当Dlx基因持续表达时，似乎完全无法发育出CD127〜+胸腺NK细胞。我们还观察到T和B细胞无法在持久性Dlx1表达的情况下发展。因此，这些研究表明Dlx TFs在淋巴细胞发育中发挥功能性作用。

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