Transcriptional regulation of macrophage polarization: enabling diversity with identity
Abstract
In terms of both phenotype and function, macrophages have remarkable heterogeneity, which reflects the specialization of tissue-resident macrophages in microenvironments as different as liver, brain and bone. Also, marked changes in the activity and gene expression programmes of macrophages can occur when they come into contact with invading microorganisms or injured tissues. Therefore, the macrophage lineage includes a remarkable diversity of cells with different functions and functional states that are specified by a complex interplay between microenvironmental signals and a hardwired differentiation programme that determines macrophage identity. In this Review, we summarize the current knowledge of transcriptional and chromatin-mediated control of macrophage polarization in physiology and disease.
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MAPK signaling cascades are the central pathway in the M1 polarization of macrophages.
“previous studies have reported that MAPK signaling cascades are the central pathway in the M1 polarization of macrophages.24,25”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [24]
During the transition to chronic FBR, macrophages switch from a pro-inflammatory M1 phenotype to an anti-inflammatory and tissue generation M2 phenotype.
“During the transition to the chronic stage of FBR macrophages switch from a pro-inflammatory activation phenotype (M1 macrophages) to an anti-inflammatory and tissue generation phenotype (M2 macrophages) (Mantovani et al., 2004; Lawrence and Natoli, 2011; Sridharan et al., 2015).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Lawrence and Natoli, 2011
MCSF receptor activates IRF4 transcription factor to promote M2 differentiation of macrophages.
“Lawrence et al has suggested that MCSF receptor activates IRF4 transcription factor to promote M2 differentiation of macrophages [37].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [37]
Mutually exclusive and feed-forward signaling pathways may play a role in macrophage plasticity.
“While the mechanisms that underlie this observed plasticity are not well understood, recent studies have shown that a number of mutually exclusive and feed forward signaling pathways may play a role [19].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [19]
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Ji, J., Shu, D., Zheng, M., Wang, J., Luo, C., Wang, Y., Guo, F., Zou, X., Lv, X., Li, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep24838 · Cited by 334 · see citing works
- Authors
- Lawrence, T., & Natoli, G.
- Affiliations
- Centre d’Immunologie de Marseille-Luminy (FR)
- European Institute of Oncology (IT)
- Corresponding author
- Lawrence, Toby
- Natoli, Gioacchino
- Venue
- Nature Reviews Immunology
- Published
- 2011-10-25
- Volume
- 11
- Issue
- 11
- Pages
- 750-761
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- OpenAlex
- W2081810806
- Cited by
- 2,284
- References
- 90
- Citations by year
- 2026: 124 · 2025: 147 · 2024: 194 · 2023: 180 · 2022: 190 · 2021: 203 · 2020: 158 · 2019: 139 · 2018: 149 · 2017: 166 · 2016: 165 · 2015: 158 · 2014: 140 · 2013: 108 · 2012: 58
- FWCI
- 8.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- macrophage polarization, macrophage identity, transcription factors, chromatin regulation, macrophage heterogeneity, tissue-resident macrophages, macrophage differentiation, macrophage lineage
- MeSH terms
- Interferon Regulatory Factor-4, Gene Expression Regulation, Humans, Macrophages, Promoter Regions, Genetic, Protein Binding, PPAR gamma, STAT1 Transcription Factor, STAT6 Transcription Factor, Interferon Regulatory Factors
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