Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23.

Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23.
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介导复合物亚基 23 对 iNKT 细胞终末成熟的调节。

DOI:
10.1038/s41467-018-06372-1
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发表时间:
2018-09-24
影响因子:
16.6
通讯作者:
Liu X
Liu X
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Xu Y;Sun Y;Shen H;Dai Y;Liu H;Li R;Zhang H;Wu L;Zhu X;Liu X

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不变的自然杀伤T细胞(iNKT细胞)是识别糖脂抗原并在激活后迅速发挥效应子功能的T细胞的特定子集。这种独特的功能是在iNKT细胞发育过程中建立的;然而,这一过程的详细机制仍有待阐明。在这里,作者表明,在CD4 + CD8+双阳性(DP)胸腺细胞中缺失介体亚基Med23完全阻断了第2阶段iNKT细胞的发育。这种失调伴随着与转录和代谢调节相关的基因表达的偏差,以及细胞的功能损害,包括NK细胞特征的丧失、分泌细胞因子的能力降低和活化后募集能力减弱。此外,Med23缺陷型iNKT细胞表现出受损的抗肿瘤活性。我们的研究确定Med23作为控制iNKT细胞分化和终末成熟的重要转录调节因子。恒定自然杀伤T细胞(iNKT)在激活后迅速发挥效应功能,但其功能成熟的机制仍有待确定。在这里,Xu及其同事表明介体亚基Med23是控制iNKT细胞终末成熟的转录调节因子。
Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4+CD8+ double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation. Invariant Natural Killer T cells (iNKT) rapidly exert effector functions upon activation, but the mechanisms of their functional maturation remain to be determined. Here, Xu and colleagues show that the mediator subunit Med23 is a transcriptional regulator controlling iNKT cell terminal maturation.
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