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VOLUME 4 , ISSUE 1 ( January-March, 2025 ) > List of Articles

REVIEW ARTICLE

Epigenetic Regulation of Macrophage Polarization

Srijan Singh, Akhil Maheshwari

Keywords : Epigenetics, Hematopoiesis, Hematopoietic stem cells, Infant, Lineage-determining transcription factors, Macrophages, Macrophage polarization states, Monocytes, Neonate, Newborn

Citation Information : Singh S, Maheshwari A. Epigenetic Regulation of Macrophage Polarization. 2025; 4 (1):36-48.

DOI: 10.5005/jp-journals-11002-0118

License: CC BY-NC 4.0

Published Online: 25-03-2025

Copyright Statement:  Copyright © 2025; The Author(s).


Abstract

Increasing data shows that macrophages, the primary immune cells in the growing fetus/neonate, retain an innate immune memory of prior stimuli. This memory is rooted in epigenetic regulation of lineage- and tissue-specific transcription either to enhance the responses or to induce tolerance to repeated exposures to a stimulus. As we understand, epigenetics refers to the study of heritable information transmitted during cell divisions that can alter gene expression via inclusion of chemical tags but no changes in the DNA sequence. We now recognize the lineage-determining transcription factors as important mediators that can make the local chromatin more accessible to other factors; one example is the erythroblast transformation-specific gene PU.1 (purine-rich sequence binding protein 1). The PU.1 can upregulate the basal activation state of many promoters by increasing histone H3 lysine 4 trimethylation (H3K4me3). There are several other newly discovered regulators that perform similar regulatory roles. These mediators enhance macrophage differentiation into several phenotypes essential for host defense or tissue homeostasis in response to environmental stimuli. The two ends of this polarization spectrum include the classically-activated (M1) macrophages induced by interferon-γ and microbial products; and the alternatively-activated (M2) macrophages induced by the T-helper 2 cytokines interleukin (IL)-4 and IL-13. The M1 macrophages participate in host defense and clearing pathogens, whereas all the known subtypes of M2 cells promote resolution of inflammation and tissue repair. Maladaptive changes in macrophages can disrupt the normal sequence of immune/inflammatory responses and predispose to disease states. The review summarizes our current understanding of the involved mechanisms; this information can help understand the immune responses in neonates who are yet to develop mature neutrophil function or adaptive immunity and are largely dependent on mononuclear cells for immune defenses.

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