The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles inmonopoiesis are largely unknown. Here, we investigated the roles of C/EBPβ in monopoiesis. Further subdivision of monocytes revealed that Cebpb messenger RNA was highly upregulated in Ly6C- monocytes in bone marrow. Accordingly, the number of Ly6C- monocytes was significantly reduced in Cebpb-/- mice. Bonemarrow chimera experiments and Mx1-Cre-mediated deletion of Cebpbrevealed a cellintrinsic and monocyte-specific requirement for C/EBPβ in monopoiesis. In Cebpb-/- mice, turnover of Ly6C- monocytes was highly accelerated and apoptosis of Ly6C- monocytes was increased. Expression of Csf1r, which encodes a receptor for macrophage colonystimulating factor, was significantly reducedin Ly6C- monocytes of Cebpb-/- mice. C/EBPβ bound to positive regulatory elements of Csf1r and promoted its transcription. Collectively, these results indicate that C/EBPβ is a critical factor for Ly6C- monocyte survival, at least in part through upregulation of Csf1r.
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