The Signal Transducer STAT5 Inhibits Plasmacytoid Dendritic Cell Development by Suppressing Transcription Factor IRF8
| Autor: | Yui-Hsi Wang, Xiao Feng Qin, Eiji Esashi, Yong-Jun Liu, Stephanie S. Watowich, Olivia A. Perng |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cellular differentiation
Immunology Bone Marrow Cells Plasmacytoid dendritic cell macromolecular substances Mice hemic and lymphatic diseases STAT5 Transcription Factor Animals Immunology and Allergy Cell Lineage STAT3 MOLIMMUNO Transcription factor STAT5 Cells Cultured Mice Knockout biology Multipotent Stem Cells Granulocyte-Macrophage Colony-Stimulating Factor hemic and immune systems Cell Differentiation Dendritic Cells Growth Inhibitors Cell biology Infectious Diseases fms-Like Tyrosine Kinase 3 Fms-Like Tyrosine Kinase 3 Interferon Regulatory Factors biology.protein IRF8 Signal transduction Signal Transduction |
| Zdroj: | Immunity. 28(4):509-520 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2008.02.013 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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