AUTHOR=Huang Han-Ying , Zheng Xin-Nan , Tian Lin 

TITLE=Ontogeny specification and epigenetic regulation of macrophage plasticity

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1676953

DOI=10.3389/fimmu.2025.1676953

ISSN=1664-3224

ABSTRACT=Macrophages are ubiquitously distributed across tissues, playing pivotal roles in maintaining homeostasis under physiological conditions and modulating disease progression in pathological contexts. Although the classic M1/M2 classification of macrophage polarization provides a useful framework, it significantly oversimplifies the plasticity and heterogeneity of these cells. Recent advances that combine lineage tracing with multi-omic profiling have unveiled new insights into macrophage functional specification. In this mini-review, we examine how ontogeny, environmental cues, and genetic as well as epigenetic factors converge to drive macrophage plasticity through epigenetic reprogramming. Additionally, we highlight cutting-edge in situ profiling techniques that facilitate the study of macrophages within their native tissue microenvironment. A deeper understanding of macrophage plasticity promises to elucidate fundamental regulatory mechanisms and uncover novel therapeutic targets, paving the way for transformative disease treatments.