MicroRNAs and Immunity: Tiny Players in a Big Field

Division of Biology, California Institute of Technology, 1200 East California Blvd, Pasadena, CA 91125, USA.
Immunity (Impact Factor: 21.56). 03/2007; 26(2):133-7. DOI: 10.1016/j.immuni.2007.02.005
Source: PubMed


RNA-mediated gene silencing is used by most eukaryotic organisms to modulate expression of protein-coding genes, to fight invading viruses, and to quell the spread in the genome of “parasitic” genetic mobile elements such as transposons. RNA silencing relies on a sequence-specific interaction between the target RNA (or DNA in certain cases) molecule and a small RNA incorporated into the multisubunit RNA-induced silencing (RISC) complex. Several classes of small silencing RNAs have been identified thus far including microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), transacting siRNAs (tasiRNAs), etc. They differ in length (18–30 bp) and origin but share a common set of proteins required for their function and sometimes production. This commentary will focus exclusively on the role in immunity of miRNAs, an evolutionarily conserved and abundant class of small silencing RNAs.

Download full-text


Available from: Mark P Boldin, Oct 05, 2015
1 Follower
21 Reads
  • Source
    • "Dysregulation of miRNAs has been reported in autoimmune diseases, including SLE [50] [51]. In particular, estrogen-regulated miRNAs modulate both innate and adaptive immune responses [48] [49]. In the present study, we identified three miRNAs down-regulated by 17β-estradiol, including let-7e-5p, miR-98-5p and miR-145a-5p. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The activation of IFN-α signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Many studies suggest that estrogens are closely related to the gender difference in the prevalence of SLE. However, the underlying mechanism of the interaction between estrogens and the activation of IFN-α signaling in SLE B cells remains incompletely understood. In the present study, we first found that healthy female mice showed an up-regulated type I IFN-induced gene signature in B cells compared with age-matched male mice, and in vivo study revealed that the gender difference was related to 17β-estradiol. Moreover, we found that 17β-estradiol could enhance the activation of IFN-α signaling in an ERα-dependent manner by down-regulating the expression of three microRNAs, including let-7e-5p, miR-98-5p and miR-145a-5p. These microRNAs could target the 3'UTR of the IKKε-encoding gene IKBKE directly and regulate the expression of IKKε, which can promote the activation of IFN-α signaling. In addition, compared with age-matched male mice, female mice showed a higher level of IKKε and lower levels of let-7e-5p, miR-98-5p and miR-145a-5p in B cells. Moreover, peripheral blood mononuclear cells from women showed a higher level of IKKε and lower levels of let-7e-5p, miR-98-5p and miR-145a-5p compared with those from age-matched men. These data suggest that 17β-estradiol amplifies the activation of IFN-α signaling in B cells via IKKε by down-regulating the expression of let-7e-5p, miR-98-5p and miR-145a-5p. Our findings may provide a new perspective for understanding the mechanism underlying the gender difference in the prevalence of SLE. Copyright © 2015. Published by Elsevier B.V.
    Biochimica et Biophysica Acta 04/2015; 1852(8). DOI:10.1016/j.bbadis.2015.04.019 · 4.66 Impact Factor
  • Source
    • "They can regulate target RNA either by repression or by promotion [25]. Recent studies have revealed the central role of miRNAs in innate immune responses to pathogens and a variety of stimuli [26], [27]. During infection, some microorganisms can regulate apoptosis of host immune cells by miRNAs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: MPT64 is one of the secreted proteins from Mycobacterium tuberculosis. Little is known about its role in infection by Mycobacterium tuberculosis. In this study, we demonstrated that MPT64 could dose-dependently inhibit the apoptosis of RAW264.7 macrophages induced by PPD-BCG. Quantitative real-time PCR results showed that the expression of bcl-2 increased in macrophages treated with MPT64 compared with PPD-treated cells. Furthermore, the results provided strong evidence that bcl-2 up-regulation was positively controlled by miRNA-21. Finally, NF-κB was identified as the transcription factor for miRNA-21 using a ChIP assay. It can be concluded from our study that MPT64 could inhibit the apoptosis of RAW264.7 macrophages through the NF-κB-miRNA21-Bcl-2 pathway.
    PLoS ONE 07/2014; 9(7):e100949. DOI:10.1371/journal.pone.0100949 · 3.23 Impact Factor
  • Source
    • "Some miRNAs have been reported to take part in the development and function of immune cells, such as macrophages, monocytes, and natural killer cells. Specifically, miR-146a has recently been found to play an important role in the regulation of TLR4 signaling in macrophages [29]. We thus hypothesized that miR-146a may attenuate liver I/R injury through negatively regulating the TLR signaling pathway in KCs. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A critical role of the Toll-like receptor(TLR) and its downstream molecules, including IL-1 receptor-associated kinase 1(IRAK1) and tumor necrosis factor receptor– associated factor 6(TRAF6), in the pathogenesis of liver ischemia/reperfusion (I/R) injury has been documented. Recently a microRNA, miR-146a, was identified as a potent negative regulator of the TLR signaling pathway. In this study, we investigated the role of miR-146a to attenuate TLR signaling and liver I/R injury in vivo and in vitro. miR-146a was decreased in mice Kupffer cells following hepatic I/R, whereas IRAK1 and TRAF6 increased. Overexpression of miR-146a directly decreased IRAK1 and TRAF6 expression and attenuated the release of proinflammatory cytokines through the inactivation of NF-κB P65 in hypoxia/reoxygenation (H/R)-induced macrophages, RAW264.7 cells. Knockdown experiments demonstrated that IRAK1 and TRAF6 are two potential targets for reducing the release of proinflammatory cytokines. Moreover, co-culture assays indicated that miR-146a decreases the apoptosis of hepatocytes after H/R. In vivo administration of Ago-miR-146a, a stable version of miR-146a in vivo, protected against liver injury in mice after I/R via inactivation of the TLR signaling pathway. We conclude that miR-146a ameliorates liver ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6.
    PLoS ONE 07/2014; 9(7):e101530. DOI:10.1371/journal.pone.0101530 · 3.23 Impact Factor
Show more