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J Exp Med. 2014 Jul 28;211(8):1525-31. doi: 10.1084/jem.20140570. Epub 2014 Jul 14.

Gata6 regulates aspartoacylase expression in resident peritoneal macrophages and controls their survival.

Author information

1
Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
2
Department of Medicine, Albert Einstein School of Medicine, Bronx, NY 10461.
3
Department of Cell Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ 08084.
4
Department of Pathology and Immunology and Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110 grandolph@path.wustl.edu.

Abstract

The transcription factor Gata6 regulates proliferation and differentiation of epithelial and endocrine cells and cancers. Among hematopoietic cells, Gata6 is expressed selectively in resident peritoneal macrophages. We thus examined whether the loss of Gata6 in the macrophage compartment affected peritoneal macrophages, using Lyz2-Cre x Gata6(flox/flox) mice to tackle this issue. In Lyz2-Cre x Gata6(flox/flox) mice, the resident peritoneal macrophage compartment, but not macrophages in other organs, was contracted, with only a third the normal number of macrophages remaining. Heightened rates of death explained the marked decrease in peritoneal macrophage observed. The metabolism of the remaining macrophages was skewed to favor oxidative phosphorylation and alternative activation markers were spontaneously and selectively induced in Gata6-deficient macrophages. Gene expression profiling revealed perturbed metabolic regulators, including aspartoacylase (Aspa), which facilitates generation of acetyl CoA. Mutant mice lacking functional Aspa phenocopied the higher propensity to death and led to a contraction of resident peritoneal macrophages. Thus, Gata6 regulates differentiation, metabolism, and survival of resident peritoneal macrophages.

PMID:
25024137
PMCID:
PMC4113942
DOI:
10.1084/jem.20140570
[Indexed for MEDLINE]
Free PMC Article
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