miR-155 regulates IFN-γ production in natural killer cells
miR-155 regulates IFN-γ production in natural killer cells
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DOI：
10.1182/blood-2011-12-398099
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发表时间：
2012-04-12
期刊：
影响因子：
20.3
通讯作者：
Caligiuri, Michael A.
中科院分区：
文献类型：
--
作者：
Trotta, Rossana;Chen, Li;Caligiuri, Michael A.
微小RNA（miRs）是具有重要调节功能的小的非编码RNA分子，其在调节自然杀伤（NK）细胞生物学中的作用尚未明确。在这里，我们表明，miR-155在与IL-12和IL-18共刺激后，或与IL-12和CD 16聚类后，在原代人NK细胞中协同诱导。miR-155的过表达增强了IL-12和IL-18或CD 16刺激对IFN-γ的诱导，而miR-155的敲低或其破坏抑制了单核因子和/或CD 16刺激的NK细胞中IFN-γ的诱导。发现这些对NK细胞IFN-γ表达的调节作用至少部分地通过miR-155对肌醇磷酸酶SHIP 1的直接作用介导。与此一致，我们观察到miR-155的调节覆盖了IL-12和IL-18介导的NK细胞中SHIP 1表达的调节。总的来说，我们的数据表明，miR-155的表达受到强烈诱导NK细胞中IFN-γ的刺激物如IL-12、IL-18和CD 16活化的调节，并且miR-155至少部分地通过下调SHIP 1而作为人NK细胞中IFN-γ产生的正调节剂发挥作用。这些发现可能与肿瘤疾病中靶向miR-155具有临床相关性。（血。2012; 119（15）：3478-3485）
MicroRNAs (miRs) are small, noncoding RNA molecules with important regulatory functions whose role in regulating natural killer (NK) cell biology is not well defined. Here, we show that miR-155 is synergistically induced in primary human NK cells after costimulation with IL-12 and IL-18, or with IL-12 and CD16 clustering. Overexpression of miR-155 enhanced induction of IFN-gamma by IL-12 and IL-18 or CD16 stimulation, whereas knockdown of miR-155 or its disruption suppressed IFN-gamma induction in monokine and/or CD16-stimulated NK cells. These effects on the regulation of NK cell IFN-gamma expression were found to be mediated at least in part via miR-155's direct effects on the inositol phosphatase SHIP1. Consistent with this, we observed that modulation of miR-155 overrides IL-12 and IL-18-mediated regulation of SHIP1 expression in NK cells. Collectively, our data indicate that miR-155 expression is regulated by stimuli that strongly induce IFN-gamma in NK cells such as IL-12, IL-18, and CD16 activation, and that miR-155 functions as a positive regulator of IFN-gamma production in human NK cells, at least in part via down-regulating SHIP1. These findings may have clinical relevance for targeting miR-155 in neoplastic disease. (Blood. 2012; 119(15):3478-3485)