C/EBPβ is required for survival of Ly6C^- monocytes

The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis 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. Bone marrow chimera experiments and Mx1-Cre-mediated deletion of Cebpb revealed a cell-intrinsic 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 colony-stimulating factor, was significantly reduced in 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.