Format

Send to

Choose Destination
Immunity. 2008 Apr;28(4):509-20. doi: 10.1016/j.immuni.2008.02.013. Epub 2008 Mar 13.

The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8.

Author information

1
Department of Immunology and Center for Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

The development of distinct dendritic cell (DC) subsets is regulated by cytokines. The ligand for the FMS-like tyrosine kinase 3 receptor (Flt3L) is necessary for plasmacytoid DC (pDC) and conventional DC (cDC) maturation. The cytokine GM-CSF inhibits Flt3L-driven pDC production while promoting cDC growth. We show that GM-CSF selectively utilized its signal transducer STAT5 to block Flt3L-dependent pDC development from the lineage-negative, Flt3+ (lin- Flt3+) bone-marrow subset. The signaling molecule STAT3, by contrast, was necessary for expansion of DC progenitors but not pDC maturation. In vivo, STAT5 suppressed pDC formation during repopulation of the DC compartment after bone-marrow ablation. GM-CSF-dependent STAT5 signaling rapidly extinguished pDC-related gene expression in lin- Flt3+ progenitors. Inspection of the Irf8 promoter revealed that STAT5 was recruited during GM-CSF-mediated suppression, indicating that STAT5 directly inhibited transcription of this critical pDC gene. Our results therefore show that GM-CSF controls the production of pDCs by employing STAT5 to suppress IRF8 and the pDC transcriptional network in lin- Flt3+ progenitors.

Comment in

PMID:
18342552
PMCID:
PMC2864148
DOI:
10.1016/j.immuni.2008.02.013
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center