miR-15/16 抑制记忆 T 细胞分化、细胞周期和存活。
miR-15/16 Restrain Memory T Cell Differentiation, Cell Cycle, and Survival.
机构信息
Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Virology and Immunology, Gladstone Institutes, San Francisco, CA 94158, USA.
出版信息
Cell Rep. 2019 Aug 20;28(8):2169-2181.e4. doi: 10.1016/j.celrep.2019.07.064.
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.
T 细胞的增殖、存活和分化的协调控制对于宿主抵御病原体和癌症至关重要。长寿命的记忆细胞，其前体在最初的免疫损伤过程中形成，提供了对未来遭遇的保护，而它们的产生是许多疫苗接种策略的目标。microRNAs（miRNAs）是调节网络中的关键节点，通过微调数千个基因来塑造有效的 T 细胞反应。在这里，我们使用复合条件性突变小鼠消除 T 细胞中的 miR-15/16 家族 miRNAs，结果表明 miR-15/16 限制了 T 细胞周期、存活和记忆 T 细胞分化。通过交联免疫沉淀 AGO2 分离的 RNA 的高通量测序，并结合 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、存活和记忆途径中关键基因的广泛网络来介导的。
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