STAT3 Is Required for Flt3L-Dependent Dendritic Cell Differentiation

Yasmina Laouar, Thomas Welte, Xin Yuan Fu, Richard A. Flavell

Research output: Contribution to journalArticle

239 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)903-912
Number of pages10
JournalImmunity
Volume19
Issue number6
DOIs
StatePublished - Dec 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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