Transcriptional Regulation of Macrophage Specification and Function.

differentiation; epigenetic regulation; macrophage; monocyte; transcription factors; Transcription Factors; Humans; Animals; Cell Differentiation/genetics; Cell Differentiation/immunology; Transcription Factors/metabolism; Transcription Factors/genetics; Cell Lineage; Macrophages/immunology; Macrophages/cytology; Macrophages/physiology; Gene Expression Regulation; Transcription, Genetic

Abstract :

[en] Tissue-resident and recruited macrophages are integral to organ development, homeostasis, immunity, and disease pathogenesis. Their remarkable diversity arises from distinct developmental origins, differentiation trajectories, and microenvironmental cues that shape their identity and function. Central to these processes is transcriptional regulation. In this review, we provide a comprehensive overview of the transcription factor (TF) networks that orchestrate resident tissue macrophage (RTM) differentiation from progenitor cells, imprint core macrophage identity, and drive tissue-specific functions. We first delineate the collaborative roles of lineage-determining TFs, such as PU.1 and C/EBPs, which prime macrophage progenitors for commitment. We then examine identity-imprinting TFs that establish and maintain the core macrophage program, and tissue-specific TFs that allow integration of local niche signals to tailor RTM phenotypes across organs. While the focus is on RTMs at steady state, we also highlight how RTMs can undergo transcriptional reprogramming upon tissue perturbation, and how newly recruited macrophages may engage distinct regulatory circuits upon entering diseased tissues, with tumors serving as an example.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Vanneste, Domien ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Immunophysiology

Marichal, Thomas ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Immunophysiology ; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium

Language :

English

Title :

Transcriptional Regulation of Macrophage Specification and Function.

Publication date :

18 December 2025

Journal title :

European Journal of Immunology

ISSN :

0014-2980

eISSN :

1521-4141

Publisher :

Wiley, Germany

Volume :

Issue :

Pages :

e70097

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://onlinelibrary.wiley.com/doi/pdf/10.1002/eji.70097

Available on ORBi :

since 28 January 2026

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