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Review
. 2019 Jan 29:10:15.
doi: 10.3389/fimmu.2019.00015. eCollection 2019.

Cytokine Targeting by miRNAs in Autoimmune Diseases

Affiliations
Review

Cytokine Targeting by miRNAs in Autoimmune Diseases

Valentina Salvi et al. Front Immunol. .

Abstract

Persistent and excessive cytokine production is a hallmark of autoimmune diseases and may play a role in disease pathogenesis and amplification. Therefore, cytokine neutralization is a useful therapeutic strategy to treat immune-mediated conditions. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological processes. Altered miRNA levels are observed in most autoimmune diseases and are recognized to influence autoimmunity through different mechanisms. Here, we review the impact of altered miRNA levels on the expression of cytokines that play a relevant pathogenic role in autoimmunity, namely primary pro-inflammatory cytokines, the IL-17/IL-23 axis, type I interferons and IL-10. Regulation can be either "direct" on the target cytokine, or "indirect," meaning that one given miRNA post-transcriptionally regulates the expression of a protein that in turn influences the level of the cytokine. In addition, miRNAs associated with extracellular vesicles can regulate cytokine production in neighboring cells, either post-transcriptionally or via the stimulation of innate immune RNA-sensors, such as Toll-like receptors. Because of their tremendous potential as physiological and pathological regulators, miRNAs are in the limelight as promising future biopharmaceuticals. Thus, these studies may lead in the near future to the design and testing of therapeutic miRNAs as next generation drugs to target pathogenic cytokines in autoimmunity.

Keywords: IFN; IL-17/IL-23; IL-6; MS; RA; SLE; TNF-α; psoriasis.

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Figures

Figure 1
Figure 1
Mechanisms of cytokine regulation by miRNAs. "Direct" regulation comprises targeting of cytokine mRNA and triggering of innate immune receptors leading to cytokine production. "Indirect" regulation comprises targeting of molecules that act as inducers or inhibitors of a given cytokine.

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