A type I IFN-Flt3 ligand axis augments plasmacytoid dendritic cell development from common lymphoid progenitors

J Exp Med. 2013 Nov 18;210(12):2515-22. doi: 10.1084/jem.20130536. Epub 2013 Oct 21.

Abstract

During infections and inflammation, plasmacytoid dendritic cells (pDCs) are the most potent type I interferon (IFN-I)-producing cells. However, the developmental origin of pDCs and the signals dictating pDC generation remain incompletely understood. Here, we report a synergistic role for IFN-I and Flt3 ligand (FL) in pDC development from common lymphoid progenitors (CLPs). Both conventional DCs (cDCs) and pDCs were generated from CLPs in response to FL, whereas pDC generation required higher concentrations of FL and concurrent IFN-I signaling. An absence of IFN-I receptor, impairment of IFN-I signaling, or neutralization of IFN-I significantly impeded pDC development from CLPs. Furthermore, FL induced IFN-I expression in CLPs, which in turn induced Flt3 up-regulation that facilitated survival and proliferation of CLPs, as well as their differentiation into pDCs. Collectively, these results define a critical role for the FL/IFN-I/Flt3 axis in pDC differentiation from CLPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Hematopoiesis
  • Interferon Type I / metabolism*
  • Interferon-alpha / metabolism
  • Lymphoid Progenitor Cells / cytology*
  • Lymphoid Progenitor Cells / immunology*
  • Lymphoid Progenitor Cells / metabolism
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Receptor, Interferon alpha-beta / deficiency
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / metabolism
  • Signal Transduction

Substances

  • Ifnar1 protein, mouse
  • Interferon Type I
  • Interferon-alpha
  • Membrane Proteins
  • flt3 ligand protein
  • Receptor, Interferon alpha-beta