CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages

Nat Commun. 2018 Dec 11;9(1):5279. doi: 10.1038/s41467-018-07685-x.


Regulatory mechanisms controlling the pool size of spleen dendritic cells (DC) remain incompletely understood. DCs are continuously replenished from hematopoietic stem cells, and FLT3-mediated signals cell-intrinsically regulate homeostatic expansion of spleen DCs. Here we show that combining FLT3 and CSF1R-deficiencies results in specific and complete abrogation of spleen DCs in vivo. Spatiotemporally controlled CSF1R depletion reveals a cell-extrinsic and non-hematopoietic mechanism for DC pool size regulation. Lack of CSF1R-mediated signals impedes the differentiation of spleen macrophages of embryonic origin, and the resulted macrophage depletion during development or in adult mice results in loss of DCs. Moreover, embryo-derived macrophages are important for the physiologic regeneration of DC after activation-induced depletion in situ. In summary, we show that the differentiation of DC and their regeneration relies on ontogenetically distinct spleen macrophages, thereby providing a novel regulatory principle that may also be important for the differentiation of other hematopoietic cell types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Dendritic Cells / cytology*
  • Dendritic Cells / metabolism
  • Female
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Male
  • Mice / embryology*
  • Mice / metabolism
  • Mice, Knockout
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Spleen / cytology
  • Spleen / metabolism
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism


  • Csf1r protein, mouse
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Flt3 protein, mouse
  • fms-Like Tyrosine Kinase 3