Tissue damage drives co localization of NF kB, Smad3, and Nrf2 to direct Rev erb sensitive wound repair in mouse macrophages
Although macrophages can be polarized to distinct phenotypes in vitro with individual ligands, in vivo they encounter multiple signals that control their varied functions in homeostasis, immunity, and disease. Here, we identify roles of Rev erb nuclear receptors in regulating responses of mouse macrophages to complex tissue damage signals and wound repair. Rather than reinforcing a specific program of macrophage polarization, Rev erbs repress subsets of genes that are activated by TLR ligands, IL4, TGFb, and damage associated molecular patterns (DAMPS) Unexpectedly, a complex damage signal promotes co localization of NF kB, Smad3, and Nrf2 at Rev erb sensitive enhancers and drives expression of genes characteristic of multiple polarization states in the same cells. Rev erb sensitive enhancers thereby integrate multiple damage activated signaling pathways to promote a wound repair phenotype. DOI: http:/dx.doi.org/10.7554/eLife.13024.001
eLife