title: Tissue-specific signals control reversible program of localization and functional polarization of macrophages.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Okabe
authors.affiliation: Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: ruslan.medzhitov@yale.edu.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Medzhitov
mesh_terms: D000818:Animals; D050993:GATA6 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D007070:Immunoglobulin A / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009852:Omentum / Q000166:cytology; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D050993:GATA6 Transcription Factor; C494760:Gata6 protein, mouse; D007070:Immunoglobulin A; D014212:Tretinoin