Involvement of MicroRNA in Microglia-Mediated Immune Response

Figure 1

MiRNA contribution to microglia activation phenotypes. Resting microglia cells are characterized by low expression levels of miR-155 and a relatively high expression of miR-124. In the presence of strong inflammatory stimuli, such as IFN-γ, GM-CSF, and LPS, microglia assume a classical activation phenotype (M1), characterized by the upregulation of both CD45 and MHC II, the expression of several inflammatory mediators, such as iNOS, the inflammatory cytokines IL-6 and TNF-α, the type I interferon IFN-β, and the downregulation of miR-124. MiR-155 upregulation is thought to be crucial for the establishment of this phenotype, since this miRNA directly targets several anti-inflammatory molecules, including SOCS-1. Alternatively, in the presence of TGF-β or the anti-inflammatory cytokine IL-10, a different activation phenotype is observed (M2). In this case, CD206 is upregulated at the cell surface, and anti-inflammatory molecules involved in tissue repair and angiogenesis are expressed. Moreover, most proinflammatory pathways, including those regulated by the transcription factors c-Jun and NF-κB, are inactivated, and miR-155 upregulation is not observed. Certain endogenous danger signals associated with neurodegenerative disorders, such as Aβ fibrils present in senile plaques of AD patients, can also cause microglia activation, although the exact nature of the observed phenotypic changes is yet to be fully characterized.