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Cell. 2014 May 8;157(4):832-44. doi: 10.1016/j.cell.2014.04.016. Epub 2014 May 1.

Tissue-specific signals control reversible program of localization and functional polarization of macrophages.

Author information

1
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
2
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: ruslan.medzhitov@yale.edu.

Abstract

Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible induction of diverse functional programs. Here, we identified retinoic acid as a signal that induces tissue-specific localization and functional polarization of peritoneal macrophages through the reversible induction of transcription factor GATA6. We further found that GATA6 in macrophages regulates gut IgA production through peritoneal B-1 cells. These results provide insight into the regulation of tissue-resident macrophage functional specialization by tissue-derived signals.

PMID:
24792964
PMCID:
PMC4137874
DOI:
10.1016/j.cell.2014.04.016
[Indexed for MEDLINE]
Free PMC Article

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