Non-Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

C/EBPbeta is required for survival of Ly6C- monocytes.

Abstract

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