Macrophage colony-stimulating factor induces the proliferation and survival of macrophages via a pathway involving DAP12 and β-catenin

Karel Otero, Isaiah R. Turnbull, Pietro Luigi Poliani, William Vermi, Elisa Cerutti, Taiki Aoshi, Ilaria Tassi, Toshiyuki Takai, Samuel L. Stanley, Mark Miller, Andrey S. Shaw, Marco Colonna

Research output: Contribution to journalArticlepeer-review

163 Citations (Scopus)

Abstract

Macrophage colony-stimulating factor (M-CSF) influences the proliferation and survival of mononuclear phagocytes through the receptor CSF-1R. The adaptor protein DAP12 is critical for the function of mononuclear phagocytes. DAP12-mutant mice and humans have defects in osteoclasts and microglia, as well as brain and bone abnormalities. Here we show DAP12 deficiency impaired the M-CSF-induced proliferation and survival of macrophages in vitro. DAP12-deficient mice had fewer microglia in defined central nervous system areas, and DAP12-deficient progenitors regenerated myeloid cells inefficiently after bone marrow transplantation. Signaling by M-CSF through CSF-1R induced the stabilization and nuclear translocation of β-catenin, which activated genes involved in the cell cycle. DAP12 was essential for phosphorylation and nuclear accumulation of β-catenin. Our results provide a mechanistic explanation for the many defects of DAP12-deficient mononuclear phagocytes.

Original languageEnglish
Pages (from-to)734-743
Number of pages10
JournalNature Immunology
Volume10
Issue number7
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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