The transcription factor PU.1 controls dendritic cell development and Flt3 cytokine receptor expression in a dose-dependent manner

Immunity. 2010 May 28;32(5):628-41. doi: 10.1016/j.immuni.2010.05.005.


The transcription factor PU.1 plays multiple context and concentration dependent roles in lymphoid and myeloid cell development. Here we showed that PU.1 (encoded by Sfpi1) was essential for dendritic cell (DC) development in vivo and that conditional ablation of PU.1 in defined precursors, including the common DC progenitor, blocked Flt3 ligand-induced DC generation in vitro. PU.1 was also required for the parallel granulocyte-macrophage colony stimulating factor-induced DC pathway from early hematopoietic progenitors. Molecular studies demonstrated that PU.1 directly regulated Flt3 in a concentration-dependent manner, as Sfpi1(+/-) cells displayed reduced expression of Flt3 and impaired DC formation. These studies identify PU.1 as a critical regulator of both conventional and plasmacytoid DC development and provide one mechanism how altered PU.1 concentration can have profound functional consequences for hematopoietic cell development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Membrane Proteins / drug effects
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / pharmacology
  • Trans-Activators / metabolism*
  • Trans-Activators / pharmacology


  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • flt3 ligand protein
  • proto-oncogene protein Spi-1