MafB is a conserved transcriptional regulator of macrophage development and functional identity across tissues and species

Domien Vanneste; Wen Peng; Zhuangzhuang Liu; Malik Hamaïdia; Raphaël La Rocca; Joan Abinet; Alexis Balthazar; Fabienne Perin; Alexandre Hego; Didier Cataldo; Fabrice Bureau; Philippe Compère; Bénédicte Machiels; Charlotte L Scott; Coraline Radermecker; Thomas Marichal

doi:10.1016/j.immuni.2026.01.012

MafB is a conserved transcriptional regulator of macrophage development and functional identity across tissues and species

Immunity. 2026 Mar 10;59(3):559-576.e12. doi: 10.1016/j.immuni.2026.01.012. Epub 2026 Feb 26.

Authors

Domien Vanneste¹, Wen Peng², Zhuangzhuang Liu³, Malik Hamaïdia⁴, Raphaël La Rocca², Joan Abinet², Alexis Balthazar⁵, Fabienne Perin⁶, Alexandre Hego⁷, Didier Cataldo⁶, Fabrice Bureau⁸, Philippe Compère⁹, Bénédicte Machiels⁵, Charlotte L Scott³, Coraline Radermecker², Thomas Marichal¹⁰

Affiliations

¹ Laboratory of Immunophysiology, GIGA Institute, University of Liège, Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, Liège, Belgium. Electronic address: domien.vanneste@uliege.be.
² Laboratory of Immunophysiology, GIGA Institute, University of Liège, Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
³ Laboratory of Myeloid Cell Biology in Tissue Damage and Inflammation, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Faculty of Science, Ghent University, Ghent, Belgium.
⁴ Laboratory of Cellular and Molecular Epigenetics, GIGA Institute, University of Liège, Liège, Belgium.
⁵ Faculty of Veterinary Medicine, University of Liège, Liège, Belgium; Laboratory of Immunology-Vaccinology, FARAH Institute, University of Liège, Liège, Belgium.
⁶ Laboratory of Tumor and Development Biology, GIGA Institute, University of Liège, Liège, Belgium.
⁷ In Vitro Imaging Platform, GIGA Institute, University of Liège, Liège, Belgium.
⁸ Faculty of Veterinary Medicine, University of Liège, Liège, Belgium; Laboratory of Cellular and Molecular Immunology, GIGA Institute, University of Liège, Liège, Belgium.
⁹ Laboratory of Functional and Evolutionary Morphology, FOCUS Research Unit, Department of Biology, Ecology and Evolution, University of Liège, Liège, Belgium; Center for Applied Research and Education in Microscopy (CAREM) and Biomaterials Interfaculty Center (CEIB), University of Liège, Liège, Belgium.
¹⁰ Laboratory of Immunophysiology, GIGA Institute, University of Liège, Liège, Belgium; Faculty of Veterinary Medicine, University of Liège, Liège, Belgium; Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium. Electronic address: t.marichal@uliege.be.

Abstract

Homeostatic resident tissue macrophages (RTMs) not only exhibit diversity across tissues but also share common features that are driven by conserved transcriptional programs. While the transcription factor MafB is highly expressed in macrophages, its role in establishing RTM identity and functions remains unclear. Here, we show that MafB was required for the development of bone-marrow-derived macrophages (BMDMs) and most RTMs in vivo. MafB deficiency retained RTMs in a CD52^high immature stage and disrupted global and tissue-specific identities and functions, impairing phagocytosis, splenic iron recycling, and lung, kidney, and gut physiology. Epigenetic profiling revealed that MafB directly regulated key RTM genes in mice and humans, including Csf1r, Mertk, Fcgr1, Cd163, and Zeb2. In silico analyses further demonstrated strong evolutionary conservation of MafB binding sites across vertebrates. Together, these findings establish MafB as a crucial regulator of RTM development and functional identity, linking MafB-dependent transcriptional programs with defining features of RTMs and tissue homeostasis.

Keywords: MafB; differentiation; macrophage; monocyte; phagocytosis; transcription factor; transcriptional regulation.

MeSH terms

Animals
Cell Differentiation / genetics
Gene Expression Regulation
Homeostasis
Humans
Macrophages* / immunology
Macrophages* / metabolism
Macrophages* / physiology
MafB Transcription Factor* / genetics
MafB Transcription Factor* / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Organ Specificity
Phagocytosis / genetics

Substances

MafB Transcription Factor
Mafb protein, mouse
MAFB protein, human