Transcriptional Regulation of Macrophage Polarization: Enabling Diversity with Identity

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2011 Oct 26

PMID 22025054

Citations 1103

Authors

Toby Lawrence

Gioacchino Natoli

Affiliations

Soon will be listed here.

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.

Citing Articles

Development of a macrophage polarization-modulating therapeutic agent for osteoarthritis treatment.

Wu L, Cao X, Shen B J Orthop Surg Res. 2025; 20(1):279.

PMID: 40082923 PMC: 11908040. DOI: 10.1186/s13018-025-05679-2.

Natural products for the treatment of ulcerative colitis: focus on the JAK/STAT pathway.

Long D, Mao C, Zhang W, Zhu Y, Xu Y Front Immunol. 2025; 16:1538302.

PMID: 40078988 PMC: 11897526. DOI: 10.3389/fimmu.2025.1538302.

Macrophage-targeting Antisenescence nanomedicine enables in-Situ NO induction for Gaseous and antioxidative atherosclerosis intervention.

Peng Y, Feng W, Huang H, Chen Y, Yang S Bioact Mater. 2025; 48:294-312.

PMID: 40060144 PMC: 11889351. DOI: 10.1016/j.bioactmat.2025.02.025.

Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine.

Tao G, Wang X, Wang J, Ye Y, Zhang M, Lang Y EPMA J. 2025; 16(1):67-93.

PMID: 39991102 PMC: 11842694. DOI: 10.1007/s13167-024-00394-0.

EBV-Induced LINC00944: A Driver of Oral Cancer Progression and Influencer of Macrophage Differentiation.

Srisathaporn S, Ekalaksananan T, Heawchaiyaphum C, Aromseree S, Maranon D, Altina N Cancers (Basel). 2025; 17(3).

PMID: 39941858 PMC: 11815735. DOI: 10.3390/cancers17030491.

References

Foster S, Hargreaves D, Medzhitov R . Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature. 2007; 447(7147):972-8. DOI: 10.1038/nature05836. View

Kaplan D, Shankaran V, Dighe A, STOCKERT E, Aguet M, Old L . Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A. 1998; 95(13):7556-61. PMC: 22681. DOI: 10.1073/pnas.95.13.7556. View

Geissmann F, Jung S, Littman D . Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003; 19(1):71-82. DOI: 10.1016/s1074-7613(03)00174-2. View

Ricote M, Li A, Willson T, Kelly C, Glass C . The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 1998; 391(6662):79-82. DOI: 10.1038/34178. View

Takeda K, Tanaka T, Shi W, Matsumoto M, Minami M, Kashiwamura S . Essential role of Stat6 in IL-4 signalling. Nature. 1996; 380(6575):627-30. DOI: 10.1038/380627a0. View

Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y . The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol. 2010; 11(10):936-44. DOI: 10.1038/ni.1920. View

Park C, Li S, Cha E, Schindler C . Immune response in Stat2 knockout mice. Immunity. 2001; 13(6):795-804. DOI: 10.1016/s1074-7613(00)00077-7. View

Boyle A, Davis S, Shulha H, Meltzer P, Margulies E, Weng Z . High-resolution mapping and characterization of open chromatin across the genome. Cell. 2008; 132(2):311-22. PMC: 2669738. DOI: 10.1016/j.cell.2007.12.014. View

Holtschke T, Lohler J, Kanno Y, Fehr T, Giese N, Rosenbauer F . Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene. Cell. 1996; 87(2):307-17. DOI: 10.1016/s0092-8674(00)81348-3. View

10.

De Santa F, Narang V, Yap Z, Tusi B, Burgold T, Austenaa L . Jmjd3 contributes to the control of gene expression in LPS-activated macrophages. EMBO J. 2009; 28(21):3341-52. PMC: 2752025. DOI: 10.1038/emboj.2009.271. View

11.

Stockinger S, Kastner R, Kernbauer E, Pilz A, Westermayer S, Reutterer B . Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. PLoS Pathog. 2009; 5(3):e1000355. PMC: 2654726. DOI: 10.1371/journal.ppat.1000355. View

12.

Nerlov C, Graf T . PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors. Genes Dev. 1998; 12(15):2403-12. PMC: 317050. DOI: 10.1101/gad.12.15.2403. View

13.

Gilchrist M, Thorsson V, Li B, Rust A, Korb M, Roach J . Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature. 2006; 441(7090):173-8. DOI: 10.1038/nature04768. View

14.

DeKoter R, Singh H . Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science. 2000; 288(5470):1439-41. DOI: 10.1126/science.288.5470.1439. View

15.

Ayton P, Chen E, Cleary M . Binding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein. Mol Cell Biol. 2004; 24(23):10470-8. PMC: 529055. DOI: 10.1128/MCB.24.23.10470-10478.2004. View

16.

Savitsky D, Tamura T, Yanai H, Taniguchi T . Regulation of immunity and oncogenesis by the IRF transcription factor family. Cancer Immunol Immunother. 2010; 59(4):489-510. PMC: 11030943. DOI: 10.1007/s00262-009-0804-6. View

17.

Creyghton M, Cheng A, Welstead G, Kooistra T, Carey B, Steine E . Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010; 107(50):21931-6. PMC: 3003124. DOI: 10.1073/pnas.1016071107. View

18.

Pascual G, Fong A, Ogawa S, Gamliel A, Li A, Perissi V . A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature. 2005; 437(7059):759-63. PMC: 1464798. DOI: 10.1038/nature03988. View

19.

Gordon S . The macrophage: past, present and future. Eur J Immunol. 2007; 37 Suppl 1:S9-17. DOI: 10.1002/eji.200737638. View

20.

DeNardo D, Barreto J, Andreu P, Vasquez L, Tawfik D, Kolhatkar N . CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009; 16(2):91-102. PMC: 2778576. DOI: 10.1016/j.ccr.2009.06.018. View