C/EBPβ is required for survival of Ly6C- monocytes

The transcription factor CCAAT/enhancer-binding protein beta (C/EBP beta) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis are largely unknown. Here, we investigated the roles of C/EBP beta 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/EBP beta 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/EBP beta bound to positive regulatory elements of Csf1r and promoted its transcription. Collectively, these results indicate that C/EBP beta is a critical factor for Ly6C(-) monocyte survival, at least in part through upregulation of Csf1r.