The Role of MicroRNAs in Regulatory T Cells and in the Immune Response

Tai-You Ha, Tai-You Ha

Abstract

The discovery of microRNA (miRNA) is one of the major scientific breakthroughs in recent years and has revolutionized current cell biology and medical science. miRNAs are small (19~25nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'UTR) of specific messenger RNAs (mRNAs) for degradation of translation repression. Genetic ablation of the miRNA machinery, as well as loss or degradation of certain individual miRNAs, severely compromises immune development and response, and can lead to immune disorders. Several sophisticated regulatory mechanisms are used to maintain immune homeostasis. Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. Recent publications have provided compelling evidence that miRNAs are highly expressed in Treg cells, that the expression of Foxp3 is controlled by miRNAs and that a range of miRNAs are involved in the regulation of immunity. A large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, cardiovascular disease and diabetes, as well as psychiatric and neurological diseases. Although it is still unclear how miRNA controls Treg cell development and function, recent studies certainly indicate that this topic will be the subject of further research. The specific circulating miRNA species may also be useful for the diagnosis, classification, prognosis of diseases and prediction of the therapeutic response. An explosive literature has focussed on the role of miRNA. In this review, I briefly summarize the current studies about the role of miRNAs in Treg cells and in the regulation of the innate and adaptive immune response. I also review the explosive current studies about clinical application of miRNA.

Keywords: Cancer; Immune response; MicroRNA; Regulatory T cells; Suppressor T cells.

Conflict of interest statement

The author have no financial conflict of interest.

Figures

Figure 1
Figure 1
miRNA biosynthesis pathway. miRNA are initially transcribed by RNA polymerase II as long primary miRNAs (pri-miRNA). Pri-miRNAs are cleaved in the nucleus by the RNase III enzyme Drosa-DGCR8 complex, liberating the stem loop or pre-miRNA. The protein Exportin-5 escorts the pre-miRNA to the cytoplasm, where a second RNAse enzyme, Dicer cleves the pre-miRNA to produce a miRNA duplex. From this miRNA/miRNA* duplex, the miRNAs strand is loaded iinto the RNA-induced silencing complex (RISC), and the miRNA* strand is destroyed. The final step in miRNA maturation is the loading of the miRNA strand into an Argonaute protein and destruction of the miRNA* strand. Translational repression of targeted mRNAs or mRNA degradation by RISC may occur within the P-body (For the details, see Text).
Figure 2
Figure 2
Possible effects of aberrant expression of miRNA in immune response (For the details, see Text).

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