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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GATA6 Transcription Factor / metabolism*
  • Gene Expression Regulation*
  • Immunoglobulin A / genetics
  • Macrophages, Peritoneal / cytology*
  • Macrophages, Peritoneal / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Omentum / cytology
  • Tretinoin / metabolism*


  • GATA6 Transcription Factor
  • Gata6 protein, mouse
  • Immunoglobulin A
  • Tretinoin

Associated data

  • GEO/GSE56711