Macrophage Polarization Comes of Age
Open accessAbstract
Functional polarization of macrophages into M1 or M2 cells is an operationally useful, simplified conceptual framework describing the plasticity of mononuclear phagocytes. Genetic approaches have begun to shed new light on mechanisms underlying macrophage polarization and on the actual in vivo significance of polarized M2 cells ( [this issue of Immunity]).
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M2 macrophages are involved in polarized Th2 inflammatory reactions and characterized by expression of arginase-1 and mannose and scavenger receptors.
“In contrast, M2 macrophages are involved in polarized Th2 inflammatory reactions and characterized by expression of arginase-1 and mannose and scavenger receptors [19], [20].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [19]
M1 macrophages are IL-12high, IL-23high, IL-10low; produce high levels of inducible nitric oxide synthetase; secrete inflammatory cytokines such as IL-1β, IL-6, and TNF; and are inducer and effector cells in Th1 type inflammatory responses.
“M1 macrophages are IL-12high, IL-23high, IL-10low; produce high levels of inducible nitric oxide synthetase (iNOS); secrete inflammatory cytokines such as IL-1β, IL-6, and TNF; and are inducer and effector cells in Th1 type inflammatory responses [19].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [19]
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“[ 2 ]). M2 macrophages are also important for wound healing and tissue remodeling, which follow infection or tissue injury.”
BackgroundBremnes, R. M., Al-Shibli, K. I., Dønnem, T., Sirera, R., Al‐Saad, S., Andersen, S., Stenvold, H., Camps, C., & Busund, L. (2010) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e3182037b76 · Cited by 369 · see citing works
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The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275 · see citing works
“their increased reactive oxygen species (ROS) production (40).”
BackgroundLi, Y., Yang, L., Hou, Y., Zhang, Z., Chen, M., Wang, M., Liu, J., Wang, J., Zhao, Z., Xie, C., et al. (2022) · Bioactive Materials · doi:10.1016/j.bioactmat.2022.03.021 · Cited by 283 · see citing works
“Macrophages affect inflammatory and tissue healing processes via two distinct polarization states: M1 macrophages that induce chronic inflammation and M2 macrophages that promote tissue healing and anti-inflammation [42,43].”
BackgroundHarford, K. A., Reynolds, C. M., McGillicuddy, F. C., & Roche, H. M. (2011) · Proceedings of The Nutrition Society · doi:10.1017/s0029665111000565 · Cited by 299 · see citing works
“There are two broad macrophage populations((40)) (Fig.”
London, A., Cohen, M., & Schwartz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00034 · Cited by 282 · see citing works
“…macrophages to an alternatively activated M2 phenotype associated with wound healing and immune resolution (Gordon, 2003; Gordon and Taylor, 2005; Mantovani et al., 2005; Mosser and Edwards, 2008; Auffray et al., 2009; Martinez et al., 2009; Gordon and Martinez, 2010; Sica and Mantovani, 2012).”
BackgroundSiniyeh, A. A., Alshaer, W., Elzogheir, N., Al-Holi, M., Alqudah, D. A., Abuarqoub, D., & Kwiatek, J. M. (2025) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2025.102225 · Cited by 280
“On the other side, anti-inflammatory signals like IL-4 and IL-13 originate M2 macrophages promoting tissue repair and resolution of inflammation [3,4].”
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High-Resolution Transcriptome of Human Macrophages
Beyer, M., Mallmann, M. R., Xue, J., Staratschek‐Jox, A., Vorholt, D., Krebs, W., Sommer, D. D., Sander, J., Mertens, C., Niño‐Castro, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045466 · Cited by 255 · see citing works
“2C) further demonstrated that the genes encoding for the surface molecules FCGR1A and FCGR1B (both representing CD64) and CD86, the cytokine/chemokine genes CXCL10, CXCL9, IL-1B, IL-6, CXCL11, TNF, IL-23A, and the genes encoding for the intracellular protein GBP1 were increased in M1-like macrophages, results similar…”
ResultIL-33/ST2 axis in inflammation and immunopathology
Milovanović, M., Volarević, V., Radosavljevic, G. D., Jovanović, I., Pejnovic, N. N., Arsenijević, N., & Lukić, M. L. (2012) · Immunologic Research · doi:10.1007/s12026-012-8283-9 · Cited by 256 · see citing works
Cellular and molecular pathways linking inflammation and cancer
Porta, C., Larghi, P., Rimoldi, M., Totaro, M. G., Allavena, P., Mantovani, A., & Sica, A. (2009) · Immunobiology · doi:10.1016/j.imbio.2009.06.014 · Cited by 250 · see citing works
“Indeed, in response to different microenvironmental signals macrophages can express different ‘‘polarized’’ functional programs (Mantovani et al. 2005).”
Regulation of macrophage function in tumors: the multifaceted role of NF-κB
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“It would be interesting to see if IKKβ or p50 are required for alternative activation of macrophages (as assessed by such markers as TGFβ, Fizz1, Ym1, Mgl2).(17,76,77) Neither Saccani and colleagues(47) nor Hagemann et al(46) have shown NF-κB regulates expression of M2 genes.”
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“Mirroring the Th1/Th2 nomenclature, polarized macrophages are often referred to as M1 (classical activation) and M2 (alternative activation) cells, respectively [11, 12].”
BackgroundMacrophages, Chronic Inflammation, and Insulin Resistance
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“The PRRs can also recognize pathogenassociated molecular patterns (PAMPs) on pathogens and biological allergens, including LPS, peptidoglycan, and bacterial DNA [135,136].”
BackgroundInfluentialImpaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration
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“Recent studies have demonstrated that macrophage polarization can play a pivotal role in determining their ultimate effector functions, including their ability to regulate angiogenesis (Apte et al., 2006; Kelly et al., 2007; Mantovani et al., 2005; Mosser, 2003).”
The promotion of a constructive macrophage phenotype by solubilized extracellular matrix
Sicari, B. M., Dziki, J. L., Siu, B. F., Medberry, C. J., Dearth, C. L., & Badylak, S. F. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.06.060 · Cited by 255 · see citing works
Tumor infiltrating immune cells in gliomas and meningiomas.
Domingues, P., González-Tablas, M., Otero, Á., Pascual, D., Miranda, D., Ruíz, L., Sousa, P., Ciudad, J., Gonçalves, J., Lopes, M. C., et al. (2016) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2015.07.019 · Cited by 258 · see citing works
Targeting GM-CSF in inflammatory diseases
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Diverse macrophages polarization in tumor microenvironment
Rhee, I. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0820-y · Cited by 291 · see citing works
“Macrophages generate different populations in response to these innate or adaptive signals (Mantovani et al. 2005; Martinez et al. 2008).”
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Macrophages—Key cells in the response to wear debris from joint replacements
Nich, C., Takakubo, Y., Pajarinen, J., Ainola, M., Salem, A., Sillat, T., Rao, A. J., Raška, M., Tamaki, Y., Takagi, M., et al. (2013) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34599 · Cited by 255 · see citing works
- Authors
- Mantovani, Sica, & Locati, M.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Mantovani,, Alberto
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 23
- Issue
- 4
- Pages
- 344-346
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1986736465
- Cited by
- 1,259
- References
- 0
- Citations by year
- 2026: 41 · 2025: 60 · 2024: 58 · 2023: 54 · 2022: 70 · 2021: 65 · 2020: 68 · 2019: 58 · 2018: 57 · 2017: 70 · 2016: 67 · 2015: 64 · 2014: 85 · 2013: 89 · 2012: 80
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2846 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- European Commission
- Ministero della Salute
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- macrophage polarization, M1 macrophages, M2 macrophages, mononuclear phagocytes, macrophage plasticity
- MeSH terms
- Cell Differentiation, Macrophages
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