Extracellular miRNAs as activators of innate immune receptors

Since the discovery of the existence of microRNAs (miRNAs) in body fluids, the fascinating hypothesis that extracellular miRNAs may play a role in cell-to-cell signalling started to make its own way. In this review, we summarize the current knowledge that supports the role of miRNAs in the regulation of the immune response by an unconventional mechanism based on the activation of intracellular innate immune sensors of nucleic acids, namely the Toll-like receptors (TLRs). Such a mechanism of action has been now described to amplify and influence the pathogenesis of several inflammation-dependent pathological conditions, including cancer growth and metastasis, neurodegeneration, autoimmunity and cardiovascular diseases. The available data suggest that we have only begun to touch upon a complex system that is likely to involve many receptors and molecules. These findings may help to understand the pathogenesis of immune-mediated diseases and provide the basis for the identification of new potential therapeutic targets.