Chistiakov Dimitry A, Myasoedova Veronika A, Revin Victor V, Orekhov Alexander N, Bobryshev Yuri V
Department of Basic and Applied Neurobiology, Serbsky Federal Medical Research Center of Psychiatry and Narcology, Moscow, Russia; Department of Molecular Genetic Diagnostics and Cell Biology, Institute of Pediatrics, Research Center for Children's Health, Moscow, Russia.
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia; Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia.
Immunobiology. 2018 Jan;223(1):101-111. doi: 10.1016/j.imbio.2017.10.005. Epub 2017 Oct 5.
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.
单核吞噬细胞通过参与解决组织损伤和促进伤口愈合来控制机体稳态。实际上，局部组织微环境的变化会显著影响单核细胞和巨噬细胞的功能行为。例如，在动脉粥样硬化斑块的所有进展阶段都会发生这种微环境变化。响应外源性刺激时，巨噬细胞表现出很大的表型可塑性和异质性。单核细胞暴露于炎症或抗炎条件下也会诱导其主要分化为促炎（M1）或抗炎（M2）巨噬细胞亚群，并在巨噬细胞亚群之间发生表型转换。表型转变伴随着巨噬细胞转录组和调控网络的巨大变化。干扰素调节因子（IRF）在单核细胞的造血发育、其向巨噬细胞的分化以及调节巨噬细胞成熟、表型极化、表型转换和功能中起关键作用。在9种IRF中，至少3种（IRF-1、IRF-5和IRF-8）参与促炎M1的形成，而IRF-3和IRF-4控制M2极化。IRF-2的作用取决于具体情况。IRF对巨噬细胞表型可塑性和异质性的影响是复杂的，并且在触发靶基因转录中涉及激活和抑制功能。
