MicroRNAs: Key Components of Immune Regulation

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Advances in Experimental Medicine and Biology (Impact Factor: 1.96). 01/2012; 780:15-26. DOI: 10.1007/978-1-4419-5632-3_2
Source: PubMed


The regulation of gene expression at the posttranscriptional level has revealed important control levels for genes important to the immune system. MicroRNAs (miRNAs) are small RNAs that regulate gene expression by inhibiting protein translation or by degrading the mRNA transcript. A single miRNA can potentially regulate the expression of multiple genes and the proteins encoded. MiRNA can influence molecular signaling pathways and regulate many biological processes including immune function. Although the role of miRNAs in development and oncogenesis has been well characterized, their role in the immune system has only begun to emerge. During the past few years, many miRNAs have been found to be important in the development, differentiation, survival, and function of B and T lymphocytes, dendritic cells, macrophages, and other immune cell types. We discuss here recent findings revealing important roles for miRNA in immunity and how miRNAs can regulate innate and adaptive immune responses.

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Available from: Peter D Katsikis
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    • "MicroRNA (miRNA) signaling plays an equally important role in cellular immune development. These small RNA molecules can regulate gene expression by targeted degradation of mRNA transcripts and direct inhibition of protein translation (Gracias and Katsikis, 2011). Profiling studies have revealed differential expression of miRNA species during TLR-induced signaling in human monocytes (Taganov et al., 2006), differentiation of monocyte-derived dendritic cells (Hashimi et al., 2009), and granulocyte development and function (Johnnidis et al., 2008). "
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    ABSTRACT: Epigenetic mechanisms such as DNA methylation, histone modification, and micro RNA signaling regulate the activity of the genome. Virtually all aspects of immunity involve some level of epigenetic regulation, whether it be host defense or in mediating tolerance. These processes are critically important in mediating dynamic responses to the environment over the life course of the individual, yet we are only just beginning to understand how dysregulation in these pathways may play a role in immune disease. Here, we give a brief chronological overview of epigenetic processes during immune development in health and disease.
    Full-text · Article · Oct 2014 · Journal of Reproductive Immunology
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    • "miRNAs have been shown to play an important role in immune evasion, regulation of cell cycle and in cancer progression [18], [19], [20]. HCV infection results in modulation of miRNA particularly those that control viral particle entry and propagation, thus playing an important role in host immune evasion [21]. "
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    ABSTRACT: Liver disease due to hepatitis C virus (HCV) infection is an important health problem worldwide. HCV induced changes in microRNAs (miRNA) are shown to mediate inflammation leading to liver fibrosis. Gene expression analyses identified dysregulation of miRNA-449a in HCV patients but not in alcoholic and non-alcoholic liver diseases. By sequence analysis of the promoter for YKL40, an inflammatory marker upregulated in patients with chronic liver diseases with fibrosis, adjacent binding sites for nuclear factor of Kappa B/P65 and CCAAT/enhancer-binding protein alpha (CEBPα) were identified. P65 interacted with CEBPα to co-operatively activate YKL40 expression through sequence specific DNA binding. In vitro analysis demonstrated that tumor necrosis factor alpha (TNFα) mediated YKL40 expression is regulated by miRNA-449a and its target NOTCH1 in human hepatocytes.NOTCH1 facilitated nuclear localization of P65 in response to TNFα. Further, HCV patients demonstrated upregulation of NOTCH1 along with downregulation of miRNA-449a. Taken together it is demonstrated that miRNA-449a plays an important role in modulating expression of YKL40 through targeting the components of the NOTCH signaling pathway following HCV infection. Therefore, defining transcriptional regulatory mechanisms which control inflammatory responses and fibrosis will be important towards developing strategies to prevent hepatic fibrosis especially following HCV recurrence in liver transplant recipients.
    Full-text · Article · Nov 2012 · PLoS ONE
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    • "MiRNAs have been implicated in various immune responses and are believed to be essential regulators of these processes [15]. The number of miRNAs involved in immune responses is growing, and among them, miR-155, -146a, -125b, -132, -9, -212 and -181, are the key players and are elegantly reviewed in [16] [17]. The inflammation-related miRNAs deserve attention in ALD, as the activation of the innate immune system is a hallmark of alcoholic steatohepatitis. "
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    ABSTRACT: Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and in vivo (Kupffer cells, KCs of alcohol-fed mice). Induction of miR-155 contributed to increased TNF alpha production and to the sensitization of KCs to produce more TNF alpha in response to LPS. In this paper, we summarize the current knowledge of miRNAs in ALD and also report increased expression of miR-155 and miR-132 in the total liver as well as in isolated hepatocytes and KCs of alcohol-fed mice. Our novel finding of the alcohol-induced increase of miRNAs in hepatocytes and KCs after alcohol feeding provides further insight into the evolving knowledge regarding the role of miRNAs in ALD.
    Full-text · Article · Jan 2012
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