miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation
miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation
复制标题
DOI：
10.1016/j.celrep.2017.08.065
复制
发表时间：
2017-09-12
期刊：
影响因子：
8.8
通讯作者：
Ha, Sang-Jun
中科院分区：
文献类型：
--
作者：
Ban, Young Ho;Oh, Se-Chan;Ha, Sang-Jun
microRNA（miR）-150是几种免疫细胞类型的发育调节因子，但其在CD 8（+）T细胞中的作用在很大程度上未被探索。在这里，我们表明miR-150调节记忆CD 8（+）T细胞的产生。在急性病毒感染后，miR-150敲除（KO）小鼠表现出CD 8（+）T细胞加速分化为记忆细胞，并提高了效应细胞因子的产生。此外，miR-150 KO CD 8（+）T细胞显示出增强的回忆反应，并改善了对另一种病毒和细菌感染的保护。我们发现，在miR-150 KO CD 8（+）T细胞的早期活化阶段，叉头框O 1（Foxo 1）和T细胞特异性转录因子1（TCF 1）上调，miR-150直接靶向并抑制Foxo 1。这些结果表明，miR-150介导的Foxo 1抑制调节效应细胞和记忆细胞分化之间的平衡，这可能有助于开发改进的疫苗和T细胞疗法。
MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8(+) T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8(+) T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8(+) T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8(+) T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8(+) T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics.