Abstract
Cytokines and transcription factors play key roles in dendritic cell (DC) development, yet information about regulatory interactions between these signals remains limited. Here we show that the cytokines GM-CSF and Flt3L induce the transcriptional mediators Id2 and E2-2 and control DC lineage diversification by STAT-dependent pathways. We found that STAT5 is required for tissue CD103(+) DC generation and plasmacytoid DC (pDC) suppression in steady state or response to GM-CSF. STAT5 stimulates GM-CSF-dependent expression of Id2, which controls CD103(+) DC production and pDC inhibition. By contrast, pDCs, but not CD103(+) DCs, are dependent on STAT3. Consistently, STAT3 stimulates Flt3L-responsive expression of the pDC regulator Tcf4 (E2-2). These data suggest that STATs contribute to DC development by controlling transcription factors involved in lineage differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cells, Cultured
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism
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Dendritic Cells / physiology*
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Gene Expression Regulation, Developmental / drug effects
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Inhibitor of Differentiation Protein 2 / genetics*
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Inhibitor of Differentiation Protein 2 / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Models, Biological
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Promoter Regions, Genetic / drug effects
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Promoter Regions, Genetic / genetics
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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STAT3 Transcription Factor / physiology*
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STAT5 Transcription Factor / genetics
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STAT5 Transcription Factor / metabolism
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STAT5 Transcription Factor / physiology*
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Transcription Factor 4
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Idb2 protein, mouse
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Inhibitor of Differentiation Protein 2
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Stat3 protein, mouse
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Tcf4 protein, mouse
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Transcription Factor 4
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Granulocyte-Macrophage Colony-Stimulating Factor