Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling.
Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling.
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DOI：
10.1038/ni.3419
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发表时间：
2016-05
影响因子：
30.5
通讯作者：
Hogquist KA
中科院分区：
文献类型：
--
作者：
Xing Y;Wang X;Jameson SC;Hogquist KA
积极选择发生在胸腺皮层，但关键的成熟事件发生在稍后的髓质。我们定义了T细胞获得增殖和迁移能力的精确阶段。晚期基因变化的转录组分析提示NF-κB和干扰素（IFN）信号通路的作用。缺乏IKK激酶TAK1的小鼠进行了正常的阳性选择，但在功能成熟中表现出特定的阻滞。NF-κB信号对肿瘤坏死因子（TNF）介导的死亡提供保护，并且是增殖和迁移所必需的。干扰素信号不依赖于NF-κB，但IFN-α r缺陷胸腺细胞表现出STAT1表达减少和表型异常，但能够增殖。因此，NF-κB和强直IFN信号都参与了胸腺细胞最终成熟为naïve T细胞的过程。
Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-κB and interferon (IFN) signaling. Mice lacking the IKK kinase TAK1 underwent normal positive selection, but exhibited a specific block in functional maturation. NF-κB signaling provided protection from tumor necrosis factor (TNF) mediated death, and was required for proliferation and emigration. The interferon signature was independent of NF-κB, however IFN-αR–deficient thymocytes showed reduced STAT1 expression and phenotypic abnormality, but were competent to proliferate. Thus, both NF-κB and tonic IFN signals are involved in the final maturation of thymocytes into naïve T cells.