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C/EBPβ is required for survival of Ly6C monocytes

Akihiro Tamura, Hideyo Hirai, Asumi Yokota, Naoka Kamio, Atsushi Sato, Tsukimi Shoji, Takahiro Kashiwagi, Yusuke Torikoshi, Yasuo Miura, Daniel G. Tenen and Taira Maekawa

Key Points

  • In Cebpb−/− mice, the number of Ly6C monocytes was specifically decreased in a cell-intrinsic manner due to their accelerated death.

  • C/EBPβ supports the survival of Ly6C monocytes, at least in part through direct upregulation of Csf1r.

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 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.

  • Submitted March 14, 2017.
  • Accepted August 7, 2017.
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