Cell
Volume 157, Issue 4, 8 May 2014, Pages 832-844
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Article
Tissue-Specific Signals Control Reversible Program of Localization and Functional Polarization of Macrophages

https://doi.org/10.1016/j.cell.2014.04.016Get rights and content
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Highlights

  • GATA6 regulates functional polarization of peritoneal macrophages

  • Retinoic acid is essential for GATA6 induction in peritoneal macrophage

  • GATA6 controls macrophage localization in peritoneal cavity

  • GATA6 controls IgA class switching in peritoneal B-1 cells

Summary

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.

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