MafB-restricted local monocyte proliferation precedes lung interstitial macrophage differentiation

  • Nat Immunol. 2023 Mar 16. doi: 10.1038/s41590-023-01468-3.
Domien Vanneste  #  1  2 ,  Qiang Bai  #  1  2 ,  Shakir Hasan  #  1  2  3 ,  Wen Peng  1  2 ,  Dimitri Pirottin  2  4 ,  Joey Schyns  1  2 ,  Pauline Maréchal  1  2 ,  Cecilia Ruscitti  1  2 ,  Margot Meunier  1  2 ,  Zhaoyuan Liu  5 ,  Céline Legrand  4 ,  Laurence Fievez  2  4 ,  Florent Ginhoux  5  6  7  8 ,  Coraline Radermecker  1  2 ,  Fabrice Bureau  4 ,  Thomas Marichal  9  10  11
Affiliations
  • 1. Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium.
  • 2. Faculty of Veterinary Medicine, Liège University, Liège, Belgium.
  • 3. Department of Immunology, University of Toronto, Toronto, Canada.
  • 4. Laboratory of Cellular and Molecular Immunology, GIGA Institute, Liège University, Liège, Belgium.
  • 5. Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
  • 6. Inserm U1015, Gustave Roussy, Bâtiment de Médecine Moléculaire, Villejuif, France.
  • 7. Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • 8. Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.
  • 9. Laboratory of Immunophysiology, GIGA Institute, Liège University, Liège, Belgium. [email protected].
  • 10. Faculty of Veterinary Medicine, Liège University, Liège, Belgium. [email protected].
  • 11. Walloon Excellence in Life Sciences and Biotechnology (WELBIO) Department, WEL Research Institute, Wavre, Belgium. [email protected].
  • # Contributed equally.
PMID: 36928411 DOI: 10.1038/s41590-023-01468-3
Abstract

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.

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