C/EBPβ is required for survival of Ly6C− monocytes

Abstract

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 <i>Cebpb</i> messenger RNA was highly upregulated in Ly6C^- monocytes in bone marrow. Accordingly, the number of Ly6C^- monocytes was significantly reduced in <i>Cebpb</i>^-/- mice. Bone marrow chimera experiments and <i>Mx1</i>-Cre-mediated deletion of <i>Cebpb</i> revealed a cell-intrinsic and monocyte-specific requirement for C/EBPβ in monopoiesis. In <i>Cebpb</i>^-/- mice, turnover of Ly6C^- monocytes was highly accelerated and apoptosis of Ly6C^- monocytes was increased. Expression of <i>Csf1r</i>, which encodes a receptor for macrophage colony-stimulating factor, was significantly reduced in Ly6C^- monocytes of <i>Cebpb</i>^-/- mice. C/EBPβ bound to positive regulatory elements of <i>Csf1r</i> 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 <i>Csf1r.</i>