Abstract
During 'emergency' situations such as infections, host defense requires rapid mobilization of bone marrow granulocyte progenitors. 'Steady-state' granulopoiesis is absolutely dependent on the C/EBPα transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Here we show that large numbers of granulocytes were generated from C/EBPα-deficient progenitors after cytokine stimulation in vivo. Cytokine treatment or fungal infection induced upregulation of C/EBPβ but not C/EBPα or C/EBPε transcripts in granulocyte progenitors, and C/EBPβ-deficient progenitors showed decreased emergency-induced granulopoiesis in vitro and in vivo. C/EBPβ inhibited proliferation less severely than did C/EBPα. These data suggest a critical function for C/EBPβ in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.
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Acknowledgements
We thank S. Elf, M.E. Guiney and K. Martens for assistance in animal husbandry; J. Yang and R. Hanson for assistance in procuring Cebpb−/− mice; L. Prickett for cell sorting; and G. Huang, S. Kobayashi, A. Kawasaki, D.A. Gonzalez, H. Iwasaki and all other members of the laboratories of D.G.T. and K.A. for discussions and suggestions. Supported by the National Institutes of Health (HL56745 to D.G.T.).
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Supplementary information
Supplementary Fig. 1
Serum cytokine concentrations after hydrodynamics-mediated gene transfer (PDF 88 kb)
Supplementary Fig. 2
Functional analysis of BM progenitors with or without cytokine treatment in vivo. (PDF 42 kb)
Supplementary Fig. 3
Rescue of granulopoiesis in Cebpaf/f conditional knockout mice by cytokine treatments. (PDF 97 kb)
Supplementary Fig. 4
Cebpb−/− progenitors demonstrate reduced proliferative potential in vitro (PDF 653 kb)
Supplementary Fig. 5
K562 cell lines stably expressing ER proteins fused to C/EBPα or C/EBPβ. (PDF 869 kb)
Supplementary Fig. 6
Effects of C/EBPα and C/EBPβ on cell cycle status of BAF and 32D cell lines (PDF 459 kb)
Supplementary Table 1
Differential counts of methylcellulose colony assay. (PDF 49 kb)
Supplementary Table 2
Primers and probes for quantitative PCR. (PDF 76 kb)
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Hirai, H., Zhang, P., Dayaram, T. et al. C/EBPβ is required for 'emergency' granulopoiesis. Nat Immunol 7, 732–739 (2006). https://doi.org/10.1038/ni1354
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DOI: https://doi.org/10.1038/ni1354
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