Macrophage plasticity, polarization, and function in health and disease

Shapouri‐Moghaddam, Abbas; Mohammadian, Saeed; Vazini, Hossein; Taghadosi, Mahdi; Esmaeili, Seyed‐Alireza; Mardani, Fatemeh; Seifi, Bita; Mohammadi, Asadollah; Afshari, Jalil T.; Sahebkar, Amirhossein

doi:10.1002/jcp.26429

Cited by 4,930Immune cells in cancerCardiac Fibrosis and RemodelingPhagocytosis and Immune Regulation

Macrophage plasticity, polarization, and function in health and disease

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Shapouri‐Moghaddam, Abbas, Mohammadian, Saeed, Vazini, Hossein, Taghadosi, Mahdi, Esmaeili, Seyed‐Alireza, Mardani, Fatemeh, Seifi, Bita, Mohammadi, Asadollah +2 more·2018·Journal of Cellular Physiology

DOI 10.1002/jcp.26429PMC PMC13482560

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Abstract

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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M1 macrophages produce pro-inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-23 and TNF-α.
“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]
M1 macrophages are pro-inflammatory and are polarized by LPS and/or cytokines such as IFN-γ and GM-CSF.
“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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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: Taghadosi, Mahdi
Esmaeili, Seyed‐Alireza
Mardani, Fatemeh
Mohammadi, Asadollah
Afshari, Jalil T.
Sahebkar, Amirhossein
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
DOI: 10.1002/jcp.26429
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 · 2017: 1 · 2015: 1 · 2012: 1
FWCI: 31.37
Type: journal article
Language: en
Open access: green
pmc.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
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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