Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function
Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function
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DOI：
10.1182/blood-2010-09-308064
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发表时间：
2011-04-28
期刊：
影响因子：
20.3
通讯作者：
Reith, Walter
中科院分区：
文献类型：
--
作者：
Dunand-Sauthier, Isabelle;Santiago-Raber, Marie-Laure;Reith, Walter
MicroRNAs(MiRNAs)是一种小的、非编码的RNAs，通过与其3‘非翻译区结合来调节靶mRNAs。越来越多的证据表明，microRNA-155(MiR155)在免疫系统的各种细胞类型中调节基因表达，在调节先天性和获得性免疫反应中发挥重要作用。为了确定miR155在树突状细胞中的作用，我们对其在人和小鼠树突状细胞中的表达和功能进行了详细的分析。在所测试的所有DC亚型中，miR155表达的强烈增加被发现是一个普遍的和进化上保守的特征，与不同成熟刺激激活DC有关。对miR155缺陷的DC的分析表明，miR155的诱导是有效的DC成熟所必需的，并且对于DC促进抗原特异性T细胞激活的能力至关重要。对miR155(-/-)DC和过度表达miR155的DC进行的表达谱研究，结合功能分析，显示编码转录因子c-Fos的mRNA是miR155的直接靶标。最后，所有miR155(-/-)DC的表型和功能缺陷都可以通过解除c-Fos的表达来复制。这些结果表明，miR155沉默c-Fos表达是DC成熟和功能所必需的保守过程。(血。2011；117(17)：4490-4500)
MicroRNAs (miRNAs) are small, noncoding RNAs that regulate target mRNAs by binding to their 3' untranslated regions. There is growing evidence that microRNA-155 (miR155) modulates gene expression in various cell types of the immune system and is a prominent player in the regulation of innate and adaptive immune responses. To define the role of miR155 in dendritic cells (DCs) we performed a detailed analysis of its expression and function in human and mouse DCs. A strong increase in miR155 expression was found to be a general and evolutionarily conserved feature associated with the activation of DCs by diverse maturation stimuli in all DC subtypes tested. Analysis of miR155-deficient DCs demonstrated that miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. Expression-profiling studies performed with miR155(-/-) DCs and DCs overexpressing miR155, combined with functional assays, revealed that the mRNA encoding the transcription factor c-Fos is a direct target of miR155. Finally, all of the phenotypic and functional defects exhibited by miR155(-/-) DCs could be reproduced by deregulated c-Fos expression. These results indicate that silencing of c-Fos expression by miR155 is a conserved process that is required for DC maturation and function. (Blood. 2011; 117(17):4490-4500)