miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival
miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival
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DOI：
10.1016/j.celrep.2019.07.064
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发表时间：
2019-08-20
期刊：
影响因子：
8.8
通讯作者：
Ansel, K. Mark
中科院分区：
文献类型：
--
作者：
Gagnon, John D.;Kageyama, Robin;Ansel, K. Mark
协调控制T细胞增殖、存活和分化对于保护宿主免受病原体和癌症的侵害至关重要。长寿的记忆细胞，其前体是在最初的免疫损伤过程中形成的，提供了对未来遭遇的保护，它们的产生是许多疫苗接种策略的目标。microRNA（miRNAs）是调控网络中的关键节点，通过微调数千个基因来形成有效的T细胞反应。在这里，使用复合条件突变小鼠消除T细胞中的miR-15/16家族miRNA，我们表明miR-15/16限制T细胞周期，存活和记忆T细胞分化。通过AGO 2的交联免疫沉淀分离的RNA的高通量测序结合miR-15/16缺陷型T细胞中的基因表达分析表明，这些作用是通过直接抑制细胞周期、存活和记忆关键通路内的广泛靶基因网络介导的。
Coordinate control of T cell proliferation, survival, and differentiation are essential for host protection from pathogens and cancer. Long-lived memory cells, whose precursors are formed during the initial immunological insult, provide protection from future encounters, and their generation is the goal of many vaccination strategies. microRNAs (miRNAs) are key nodes in regulatory networks that shape effective T cell responses through the fine-tuning of thousands of genes. Here, using compound conditional mutant mice to eliminate miR-15/16 family miRNAs in T cells, we show that miR-15/16 restrict T cell cycle, survival, and memory T cell differentiation. High throughput sequencing of RNA isolated by cross-linking immunoprecipitation of AGO2 combined with gene expression analysis in miR-15/16-deficient T cells indicates that these effects are mediated through the direct inhibition of an extensive network of target genes within pathways critical to cell cycle, survival, and memory.