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Macrophage plasticity, polarization, and function in health and disease
Open accessAbstract
Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro‐environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro‐inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN‐γ, GM‐CSF, and produce pro‐inflammatory cytokines such as interleukin‐1β (IL‐1β), IL‐6, IL‐12, IL‐23, and TNF‐α; and 2) Alternatively activated or M2 macrophages, which are anti‐inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL‐4 and IL‐13 and produce anti‐inflammatory cytokines such as IL‐10 and TGF‐β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation‐associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF‐α, IL‐1β, IL‐12, and IL‐23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL‐10 and TGF‐β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti‐microbial defense, anti‐tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.
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“and produce pro-inflammatory cytokines, such as interleukin-1β IL-1β, IL-6, IL-12, IL-23 and TNF-α [194].”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [194]
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“M1 macrophages are pro-inflammatory and polarized by lipopolysaccharides (LPS) and/or cytokines, such as IFN-γ and the granulocyte-macrophage colony-stimulating factor GM-CSF”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [194]
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Metadata
- Authors
- Shapouri‐Moghaddam, A., Mohammadian, S., Vazini, H., Taghadosi, M., Esmaeili, S., Mardani, F., Seifi, B., Mohammadi, A., Afshari, J. T., & Sahebkar, A.
- Affiliations
- Faculty of Medicine Department of Immunology BuAli Research Institute Mashhad University of Medical Sciences Mashhad Iran
- Faculty of Medicine Student Research Committee Immunology Research Center BuAli Research Institute Mashhad University of Medical Sciences Mashhad Iran
- Islamic Azad University of Hamedan (IR)
- Kermanshah University of Medical Sciences (IR)
- Mashhad University of Medical Sciences (IR)
- Islamic Azad University, Mashhad (IR)
- Corresponding author
- Sahebkar, Amirhossein
- ORCID
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2018-03-01
- Volume
- 233
- Issue
- 9
- Pages
- 6425-6440
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- PMC
- PMC13482560
- OpenAlex
- W2782685575
- Cited by
- 4,930
- References
- 131
- Citations by year
- 2026: 477 · 2025: 876 · 2024: 898 · 2023: 783 · 2022: 666 · 2021: 564 · 2020: 399 · 2019: 183 · 2018: 77
- FWCI
- 31.37
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- macrophages, macrophage polarization, M1 macrophages, M2 macrophages, macrophage plasticity, macrophage migration, antigen presentation, cytokine and chemokine production, macrophage metabolism, microRNA, tissue repair, inflammation, pregnancy, antimicrobial defense, antitumor immunity, obesity, asthma, allergy, atherosclerosis, fibrosis, wound healing, autoimmunity
- MeSH terms
- Animals, Cell Differentiation, Humans, Inflammation, Macrophages, Phenotype, Cytokines
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