MicroRNAs and toll-like receptor/interleukin-1 receptor signaling

The discovery of miRNAs has revolutionized the way we examine the genome, RNA products, and the regulation of transcription and translation. Their ability to modulate protein expression through mRNA degradation and translation repression resulted in avid scientific interest in miRNAs over the past decade. This research has led to findings that indicate miRNAs can regulate an array of cellular functions such as cellular apoptosis, proliferation, differentiation, and metabolism. Specifically, the capability of miRNAs to finely-tune gene expression naturally lends itself to immune system regulation which requires precise control for proper activity. In fact, abnormal miRNAs expression is often seen with inflammatory disorders like rheumatoid arthritis, systemic lupus erthematosus, experimental autoimmune encephalomyelitis, and inflammatory cancers. As a result, research investigating miRNAs modulation of immune cell proliferation, differentiation, and cellular signaling has yielded fruitful results. Specifically, in this review, we will examine the impact of miRNAs on toll-like receptor (TLRs) and interleukin-1β (IL-1β) signaling, which are integral in the proper functioning of the innate immune system. These signaling pathways share several key downstream signaling adaptors and therefore produce similar downstream effects such as the production of pro-inflammatory cytokines, chemokines, and interferons. This review will examine in depth the specific interactions of miRNAs with receptors, adaptor molecules, and regulator molecules within these cellular pathways. In addition, we will discuss the modulation of miRNAs' expression by TLR and IL-1R signaling through positive and negative feedback loops.