Figure 2. Regulation of classical and alternative macrophage activation by miRNAs.

The schematic illustrates prototypical ligand/receptor pairs that stimulate either the alternative (or M2; left, blue) or the classical (or M1; right, pink) activation of macrophages. Several miRNAs are induced upon either type of macrophage activation. These include miRNAs that primarily sustain classical activation (pink-shaded contours) either by enhancing proinflammatory signaling (e.g., miR-155, miR-125a/b) or by attenuating alternative activation (e.g., miR-511-3p, miR-378 and miR-155). Other miRNAs conversely attenuate classical activation (blue-shaded contours) by repressing several positive regulators of proinflammatory signaling (e.g., miR-146a, miR187 and Let-7e). Note that miR-155 may also function as a negative regulator of proinflammatory signaling (not depicted; see main text). Signaling molecules implicated in classical versus alternative activation of macrophages, and related to miRNAs, are discussed in the main text.