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The mononuclear phagocytes control the body homeostasis through the involvement in resolving tissue injury and further wound healing. Indeed, local tissue microenvironmental changes can significantly influence the functional behavior of monocytes and macrophages. Such microenvironmental changes for example occur in an atherosclerotic plaque during all progression stages. In response to exogenous stimuli, macrophages show a great phenotypic plasticity and heterogeneity. Exposure of monocytes to inflammatory or anti-inflammatory conditions also induces predominant differentiation to proinflammatory (M1) or anti-inflammatory (M2) macrophage subsets and phenotype switch between macrophage subsets. The phenotype transition is accompanied with great changes in the macrophage transcriptome and regulatory networks. Interferon-regulatory factors (IRFs) play a key role in hematopoietic …