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.

中文翻译：

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介体复合物亚基23对iNKT细胞终末成熟的调节。

不变的自然杀伤性T细胞（iNKT细胞）是识别糖脂抗原的T细胞的特定子集，并在激活后迅速发挥效应子功能。这种独特的功能是在iNKT细胞发育过程中建立的。但是，此过程的详细机制仍有待阐明。在这里，作者表明CD4 ⁺ CD8 ⁺中介体亚基Med23的缺失双阳性（DP）胸腺细胞在第2阶段完全阻断了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出现偏差，以及细胞功能受损，包括NK细胞特性的丧失，激活后降低了分泌细胞因子的能力并减弱了募集能力。此外，Med23缺陷的iNKT细胞表现出受损的抗肿瘤活性。我们的研究确定Med23是控制iNKT细胞分化和终末成熟的重要转录调节因子。