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首页> 外文期刊>Immunity >The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15
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The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15

机译：螺旋环螺旋蛋白ID2通过调节其对白介素15的敏感性来控制NK细胞的命运。

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摘要

The inhibitor of DNA binding 2 (Id2) is essential for natural killer (NK) cell development with its canonical role being to antagonize E-protein function and alternate lineage fate. Here we have identified a key role for Id2 in regulating interleukin-15 (IL-15) receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Id2 deletion in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling and metabolic function and this could be rescued by strong IL-15 receptor stimulation or genetic ablation of Socs3. During NK cell maturation, we observed an inverse correlation between E-protein target genes and Id2. These results shift the current paradigm on the role of ID2, indicating that it is required not only to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15.
机译：DNA结合2（Id2）抑制剂对于自然杀伤（NK）细胞发育至关重要，其典型作用是拮抗E蛋白功能和替代谱系命运。在这里，我们已经确定了Id2在通过抑制包括Socs3在内的多个E蛋白靶基因来调节白细胞介素15（IL-15）受体信号传导和NK细胞稳态中的关键作用。成熟的NK细胞中的Id2缺失由于IL-15受体信号传导和代谢功能受损而与其体内稳态不相容，可以通过强烈的IL-15受体刺激或Socs3的遗传切除来挽救。在NK细胞成熟过程中，我们观察到E蛋白靶基因与Id2之间呈负相关。这些结果改变了当前关于ID2作用的范式，表明不仅需要在NK细胞定殖期间拮抗E蛋白，而且还经常需要滴定E蛋白活性以调节NK细胞适应性和对IL-15的反应性。

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