[en] 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 CD52high 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.
Research Center/Unit :
GIGA-I3 - Giga-Infection, Immunity and Inflammation - ULiège
Disciplines :
Life sciences: Multidisciplinary, general & others
Liu, Zhuangzhuang; 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
Hamaïdia, Malik ; Université de Liège - ULiège > Département GxABT > Microbial technologies
La Rocca, Raphaël ; Université de Liège - ULiège > Molecular Systems (MolSys)
Balthazar, Alexis ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Perin, Fabienne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Hego, Alexandre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et pathologiques
Bureau, Fabrice ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Cellular and Molecular Immunology
Compère, Philippe ; Université de Liège - ULiège > Département de Biologie, Ecologie et Evolution
Machiels, Bénédicte ; Université de Liège - ULiège > Département des maladies infectieuses et parasitaires (DMI) > Vaccinologie vétérinaire
Scott, Charlotte L; 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
HE - 101124390 - MoMacTrajectALI - Monocyte-to-Macrophage Trajectories After Lung Injury: Spatio-temporal investigation, molecular regulation & functional implications for lung regeneration and immunity
Funders :
ERDF - European Regional Development Fund Leon Fredericq Foundation Fonds Baillet Latour ERC - European Research Council F.R.S.-FNRS - Fund for Scientific Research ULiège - University of Liège European Union
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