A microRNA circuitry links macrophage polarization to metabolic homeostasis.

Macrophages play an important role in tissue repair and remodeling and innate immune response. Tissue macrophages are highly heterogeneous and can undergo 2 distinct programs of functional specification termed classical (M1) and alternative (M2) activation.1,2 In response to signals elicited by bacterial infections, such as lipopolysaccharide (LPS) and interferon, macrophages adopt a proinflammatory phenotype and contribute to defense against invading pathogens through phagocytosis, bactericidal activity, and the secretion of proinflammatory cytokines and chemokines. In contrast, interleukin-4 (IL-4) and IL-13 promote alternative activation of macrophages that favors tissue remodeling and repair, parasite elimination, and tumor progression. At the molecular level, M1 and M2 macrophages express unique cell surface markers and secrete distinct sets of effector molecules. Classically activated macrophages secrete proinflammatory cytokines, such as tumor necrosis factor , IL-1 , and IL-6, and produce reactive oxygen species and nitric oxide, whereas alternatively activated macrophages preferentially synthesize anti-inflammatory cytokines such as IL-10 and have subdued proinflammatory cytokine gene expression. A balance between classical and alternative macrophage activation serves to maintain tissue homeostasis and host defense.