The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity
The mediator subunit Med23 contributes to controlling T-cell activation and prevents autoimmunity
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DOI：
10.1038/ncomms6225
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发表时间：
2014-10
影响因子：
16.6
通讯作者：
Yang Sun;Xiaoyan Zhu;Xufeng Chen;Haifeng Liu;Yu Xu;Yajing Chu;Gang Wang;Xiaolong Liu
中科院分区：
文献类型：
--
作者：
Yang Sun;Xiaoyan Zhu;Xufeng Chen;Haifeng Liu;Yu Xu;Yajing Chu;Gang Wang;Xiaolong Liu
T细胞活化对于成功的免疫应答至关重要，并且在多个水平上受到控制。尽管T细胞受体相关信号分子的许多变化影响T细胞活化，但控制这一过程的转录机制在很大程度上仍然未知。在这里，我们发现，T细胞特异性介体亚基Med23的缺失导致T细胞的过度活化和老年Med23缺陷小鼠表现出自身免疫综合征。Med23特异性且一致地促进T细胞活化的多个负调节因子的转录。在不存在Med23的情况下，T细胞活化阈值较低，这导致增强的抗肿瘤T细胞功能。累积起来，我们的数据表明，Med23有助于在转录水平上控制T细胞活化，并防止自身免疫的发展。
T-cell activation is critical for successful immune responses and is controlled at multiple levels. Although many changes of T-cell receptor-associated signalling molecules affect T-cell activation, the transcriptional mechanisms that control this process remain largely unknown. Here we find that T cell-specific deletion of the mediator subunit Med23 leads to hyperactivation of T cells and aged Med23-deficient mice exhibit an autoimmune syndrome. Med23 specifically and consistently promotes the transcription of multiple negative regulators of T-cell activation. In the absence of Med23, the T-cell activation threshold is lower, which results in enhanced antitumour T-cell function. Cumulatively, our data suggest that Med23 contributes to controlling T-cell activation at the transcriptional level and prevents the development of autoimmunity.