Mafb protein, mouse; MafB Transcription Factor; Animals; Mice; Cell Differentiation; Lung; Cell Proliferation; MafB Transcription Factor/genetics; Monocytes; Macrophages; Immunology and Allergy; Immunology
[en] Resident tissue macrophages (RTMs) are differentiated immune cells that populate distinct niches and exert important tissue-supportive functions. RTM maintenance is thought to rely either on differentiation from monocytes or on RTM self-renewal. Here, we used a mouse model of inducible lung interstitial macrophage (IM) niche depletion and refilling to investigate the development of IMs in vivo. Using time-course single-cell RNA-sequencing analyses, bone marrow chimeras and gene targeting, we found that engrafted Ly6C+ classical monocytes proliferated locally in a Csf1 receptor-dependent manner before differentiating into IMs. The transition from monocyte proliferation toward IM subset specification was controlled by the transcription factor MafB, while c-Maf specifically regulated the identity of the CD206+ IM subset. Our data provide evidence that, in the mononuclear phagocyte system, the ability to proliferate is not merely restricted to myeloid progenitor cells and mature RTMs but is also a tightly regulated capability of monocytes developing into RTMs in vivo.
Funding text :
We thank all members of the Immunophysiology and Cellular and Molecular Immunology laboratories (GIGA Institute, Liège, Belgium) for discussions; S. Ormenese, R. Stefan, A. Hego, G. Lefevre and C. Vanwinge from the GIGA In Vitro Imaging Platform; P. Drion, G. Lambert, L. B. Remy and all staff members from the GIGA Mouse facility and Transgenics Platform; W. Coppieters, L. Karim, M. Deckers, A. Mayer, A. Lavergne and members from the GIGA Genomics Platform; and R. Fares, I. Sbai and A. Lio for their excellent administrative support. T.M. acknowledges support from the F.R.S-FNRS (Incentive Grant for Scientific Research), from the FRFS-Welbio and from the Acteria Foundation. T.M. is supported by a Research Project Grant of the F.R.S.-FNRS, by a FRFS-Welbio Advanced Grant (WELBIO-CR-2022A-10), by an ERC Starting Grant (ERC StG 2018 IM-ID: 801823), by the Baillet Latour Fund, by an ‘Action de Recherche Concertée de la Fédération Wallonie-Bruxelles de Belgique’ and by the Léon Fredericq Foundation; F.B. acknowledges support from the FRFS-Welbio and is supported by an Excellence of Science (EOS) program from the F.R.S.-FNRS and FWO; S.H. received a postdoctoral fellowship from Wallonie-Bruxelles International (WBI); D.V. and C. Ruscitti are research fellows of the F.R.S.-FNRS; W.P. is supported by a fellowship of the China Scholarship Council (CSC); M.M. is a research fellow of the FRIA – FNRS. C. Radermecker is a ‘Chargé de Recherches’ of the F.R.S.-FNRS.