C/EBPβ mediates the differentiation of peritoneal, but not splenic or liver, tissue macrophages (153.28)

Abstract

Abstract Macrophages are dispersed throughout the body but exhibit tissue-specific phenotypes and functions. The extracellular and transcriptional pathways that regulate the generation of tissue-specific macrophages are largely unknown. In mice, the peritoneal cavity contains two distinct populations of macrophages, small (CD11b+F4/80lowCD93-) and large (CD11b+F4/80hiCD93+) peritoneal macrophages (SPM and LPM, respectively). Here, we show that mice deficient for the transcription factor C/EBPβ have increased numbers of SPM compared to control littermates, but lack LPM. In C/EBPβ-sufficient and deficient mice, however, splenic (MOMA-1+ and F4/80+) and liver (F4/80+) macrophage compartments are equivalent. When adoptively transferred into C/EBPβ-/- mice, wild-type SPM give rise to LPM, revealing a differentiative pathway from SPM to LPM that requires C/EBPβ. A role for C/EBPβ in the differentiation of certain macrophages is also evident in vitro, as bone marrow cells from C/EBPβ-sufficient and -deficient mice produce macrophages equivalently in cultures containing M-CSF, but C/EBPβ-/- bone marrow cells fail to generate normal macrophages in GM-CSF cultures. These findings demonstrate that tissue-specific macrophages arise through distinct transcriptional pathways, and reveal C/EBPβ as a master regulator of differentiation for a restricted subset of tissue macrophages.