Wang Aibo, Ding Xiao, Demarque Maud, Liu Xindong, Pan Deng, Xin Huawei, Zhong Bo, Wang Xiaohu, Dejean Anne, Jin Wei, Dong Chen
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Nuclear Organization and Oncogenesis Laboratory, Department of Cell Biology and Infection, INSERM U993, Institute Pasteur, 75015 Paris, France.
J Immunol. 2017 May 1;198(9):3461-3470. doi: 10.4049/jimmunol.1600980. Epub 2017 Mar 17.
SUMOylation is an important posttranslational modification that regulates protein function in diverse biological processes. However, its role in early T cell development has not been genetically studied. UBC9 is the only E2 enzyme for all SUMOylation. In this study, by selectively deleting gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss of results in a significant reduction of CD4 and CD8 single-positive lymphocytes in both thymus and periphery. -deficient cells exhibit defective late-stage maturation post the initial positive selection with increased apoptosis and impaired proliferation, among which attenuated IL-7 signaling was correlated with the decreased survival of -deficent CD8 single-positive cells. Furthermore, NFAT nuclear retention induced by TCR signals was regulated by SUMOylation during thymocytes development. Our study thus reveals a novel posttranslational mechanism underlying T cell development.
SUMO化是一种重要的翻译后修饰，可在多种生物学过程中调节蛋白质功能。然而，其在早期T细胞发育中的作用尚未进行遗传学研究。UBC9是所有SUMO化过程中唯一的E2酶。在本研究中，通过在T细胞中选择性删除基因，我们研究了SUMO化在T细胞发育中的功能作用。基因缺失导致胸腺和外周血中CD4和CD8单阳性淋巴细胞显著减少。基因缺陷细胞在初始阳性选择后的晚期成熟过程中表现出缺陷，凋亡增加且增殖受损，其中IL-7信号减弱与基因缺陷的CD8单阳性细胞存活率降低相关。此外，在胸腺细胞发育过程中，TCR信号诱导的NFAT核滞留受SUMO化调节。因此，我们的研究揭示了T细胞发育背后一种新的翻译后机制。
