A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential

Immunity. 2013 May 23;38(5):943-57. doi: 10.1016/j.immuni.2013.04.006. Epub 2013 Apr 25.

Abstract

Macrophage and dendritic cell (DC) progenitors (MDPs) and common DC progenitors (CDPs) are bone marrow (BM) progenitors with DC differentiation potential. However, both MDPs and CDPs give rise to large numbers of conventional DCs (cDCs) and few plasmacytoid DCs (pDCs), implying that more dedicated pDC progenitors remain to be identified. Here we have described DC progenitors with a prominent pDC differentiation potential. Although both MDPs and CDPs express the macrophage colony stimulating factor (M-CSF) receptor (M-CSFR), the progenitors were confined to a M-CSFR(-) fraction, identified as Lin(-)c-Kit(int/lo)Flt3(+)M-CSFR(-), and expressed high amounts of E2-2 (also known as Tcf4) an essential transcription factor for pDC development. Importantly, they appeared to be directly derived from either CDPs or lymphoid-primed multipotent progenitors (LMPPs). Collectively, our findings provide insight into DC differentiation pathways and may lead to progenitor-based therapeutic applications for infection and autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / biosynthesis
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Lymphoid Progenitor Cells / immunology
  • Lymphoid Progenitor Cells / metabolism*
  • Lymphopoiesis / genetics
  • Lymphopoiesis / immunology*
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptor, Macrophage Colony-Stimulating Factor* / biosynthesis
  • Receptor, Macrophage Colony-Stimulating Factor* / deficiency
  • Receptor, Macrophage Colony-Stimulating Factor* / genetics
  • Receptor, Macrophage Colony-Stimulating Factor* / metabolism
  • Transcription Factor 4
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Tcf4 protein, mouse
  • Transcription Factor 4
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Flt3 protein, mouse
  • Receptor, Macrophage Colony-Stimulating Factor
  • fms-Like Tyrosine Kinase 3