The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2

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 (Figure). This review characterizes the roles of interferon-regulatory factors in the polarization of non-activated macrophages (M0) to M1 and M2 macrophages. [Display omitted] •Exposure of monocytes to inflammatory or anti-inflammatory conditions induces differentiation to M1 or M2 subsets.•Exposure of monocytes to inflammatory or anti-inflammatory conditions leads to phenotype switch between macrophage subsets.•IRFs play a key role in c development of monocytes, their differentiation to macrophages.•Impact of IRFs on macrophage phenotype plasticity and heterogeneity is complex.•IRFs involves activating and repressive function in triggering transcription of target genes. 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 development of monocytes, their differentiation to macrophages, and regulating macrophage maturation, phenotypic polarization, phenotypic switch, and function. Of 9 IRFs, at least 3 (IRF-1, IRF-5, and IRF-8) are involved in the commitment of proinflammatory M1 whereas IRF-3 and IRF-4 control M2 polarization. The role of IRF-2 is context-dependent. The IRF impact on macrophage phenotype plasticity and heterogeneity is complex and involves activating and repressive function in triggering transcription of target genes.