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.

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    • "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. "
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    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
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    • "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. "
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    PLoS ONE 07/2014; 9(7):e100949. DOI:10.1371/journal.pone.0100949 · 3.23 Impact Factor
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    • "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. "
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