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The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2
Dimitry A Chistiakov1, Veronika A Myasoedova2, Victor V Revin3
1Department 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.
Abstract:
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.
Insights
Mononuclear phagocytes, including monocytes and macrophages, are crucial for tissue repair. Interferon-regulatory factors (IRFs) significantly influence macrophage polarization and function, impacting inflammatory responses and homeostasis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Mononuclear phagocytes (monocytes and macrophages) maintain tissue homeostasis and wound healing.
- Local microenvironments, such as atherosclerotic plaques, critically influence macrophage function.
- Macrophages exhibit significant phenotypic plasticity and heterogeneity in response to stimuli.
Purpose of the Study:
- To elucidate the role of Interferon-regulatory factors (IRFs) in regulating macrophage phenotype plasticity and heterogeneity.
- To understand how IRFs control monocyte differentiation, macrophage maturation, and polarization into M1 (proinflammatory) and M2 (anti-inflammatory) subsets.
Main Methods:
- Analysis of the role of specific IRFs (IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF-8) in macrophage polarization.
- Investigating the impact of IRFs on macrophage transcriptome and regulatory networks during phenotype transitions.
Main Results:
- IRF-1, IRF-5, and IRF-8 are implicated in M1 proinflammatory macrophage commitment.
- IRF-3 and IRF-4 are key regulators of M2 anti-inflammatory macrophage polarization.
- IRF-2 exhibits context-dependent functions in macrophage polarization.
Conclusions:
- Interferon-regulatory factors (IRFs) play a complex and critical role in governing macrophage phenotype plasticity and heterogeneity.
- IRFs exert both activating and repressive transcriptional control, shaping macrophage responses in diverse physiological and pathological conditions.
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