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MafB-restricted local monocyte proliferation precedes lung interstitial macrophage differentiation.

  • Vanneste, Domien
  • Bai, Qiang
  • Hasan, Shakir
  • Peng, Wen
  • Pirottin, Dimitri
  • Schyns, Joey
  • Maréchal, Pauline
  • Ruscitti, Cecilia
  • Meunier, Margot
  • Liu, Zhaoyuan
  • Legrand, Céline
  • Fievez, Laurence
  • Ginhoux, Florent
  • Radermecker, Coraline
  • Bureau, Fabrice
  • Marichal, Thomas
Publication Date
Mar 01, 2023
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peer reviewed / 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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