Role of microRNAs in the regulation of innate immune cells under neuroinflammatory conditions

• Transcriptome studies suggest miRNAs can be used as microglia phenotype markers.
• MiR-124 regulates the quiescent state of microglia in the brain.
• The immune role of miR-146a and miR-155 depends on the type of brain injury.
• Transcription kinetics of miRNAs/target mRNAs control miRNA immune regulatory role.

MiRNAs are short, evolutionary conserved noncoding RNA molecules with the ability to control the magnitude of inflammation. The immunosuppressive nature of the brain is sustained by miRNA-dependent regulation of microglial cells, which become activated under neuroinflammatory conditions, such as brain injury and neurodegeneration. The pro-inflammatory and suppressive role of the most studied neuroimmune miRNAs, miR-155 and miR-146a, has been recently challenged. Although the molecular targets of these miRNAs remain unchanged across brain diseases, different kinetics of miRNA expression and degradation can produce different immune outcomes and change microglia phenotypes. Here, we discuss current knowledge regarding the implications of disruption of miRNA networks in neuroinflammation and in the pathophysiology of acute and chronic CNS diseases.