STAT3 is required for Flt3L-dependent dendritic cell differentiation

Immunity. 2003 Dec;19(6):903-12. doi: 10.1016/s1074-7613(03)00332-7.


The signals that control decisions of progenitor commitment involve the interplay of both cytokines and transcription factors. Flt3L has emerged as a potential regulator of dendritic cell (DC) development, but regulation of HSC commitment to the DC lineage remains poorly understood. Our central finding is the identification of STAT3 activation as a checkpoint of Flt3L-regulated DC development. Deletion of STAT3 caused profound deficiency in the DC compartment and abrogated Flt3L effects on DC development. DC derivation by Flt3L revealed a normal HSC pool, a 2- to 3-fold accumulation of CLP/CMP, but absence of common DC precursors as well as their DC progeny in STAT3-deficient mice. The formation of CMP and CLP represents the first decisive lineage commitment step, and in this regard we provide evidence that commitments of CLP/CMP to the DC lineage strictly depend on the interplay of both Flt3L and STAT3 activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / metabolism*
  • Dendritic Cells / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Homeostasis
  • Membrane Proteins / metabolism*
  • Mice
  • STAT3 Transcription Factor
  • Trans-Activators / deficiency
  • Trans-Activators / metabolism*


  • DNA-Binding Proteins
  • Membrane Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • flt3 ligand protein
  • Granulocyte-Macrophage Colony-Stimulating Factor