Nature Immunology 7, 732 - 739 (2006)
Published online: 4 June 2006; | doi:10.1038/ni1354
C/EBP is required for 'emergency' granulopoiesisHideyo Hirai1, 2, Pu Zhang1, Tajhal Dayaram1, Christopher J Hetherington1, Shin-ichi Mizuno3, Jiro Imanishi2, Koichi Akashi3, 4
& Daniel G Tenen11
Harvard Institutes of Medicine and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA. 2
Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan. 3
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. 4
Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka 812-0034, Japan.
Correspondence should be addressed to Daniel G Tenen dtenen@bidmc.harvard.edu 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/EBP transcription factor, but the transcriptional mechanisms underlying emergency granulopoiesis remain unclear. Here we show that large numbers of granulocytes were generated from C/EBP-deficient progenitors after cytokine stimulation in vivo. Cytokine treatment or fungal infection induced upregulation of C/EBP but not C/EBP or C/EBP transcripts in granulocyte progenitors, and C/EBP-deficient progenitors showed decreased emergency-induced granulopoiesis in vitro and in vivo. C/EBP inhibited proliferation less severely than did C/EBP. These data suggest a critical function for C/EBP in emergency granulopoiesis, which demands both differentiation and proliferation of granulocyte precursors.
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