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Nature Immunology 7, 732–739 (1 July 2006) | doi:10.1038/ni1354

C/EBP|[beta]| is required for 'emergency' granulopoiesis

Hideyo Hirai , Pu Zhang , Tajhal Dayaram , Christopher J Hetherington , Shin-ichi Mizuno , Jiro Imanishi , Koichi Akashi & Daniel G Tenen

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/EBP|[epsi]| 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.