In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-07-27)
Abstract:
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, TGFβ, and damage-associated molecular patterns (DAMPS). Unexpectedly, a complex damage signal promotes co-localization of NF-κB, 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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.13024.001
DOI:
10.7554/eLife.13024.002
DOI:
10.7554/eLife.13024.003
DOI:
10.7554/eLife.13024.004
DOI:
10.7554/eLife.13024.005
DOI:
10.7554/eLife.13024.006
DOI:
10.7554/eLife.13024.007
DOI:
10.7554/eLife.13024.008
DOI:
10.7554/eLife.13024.009
DOI:
10.7554/eLife.13024.010
DOI:
10.7554/eLife.13024.011
DOI:
10.7554/eLife.13024.012
DOI:
10.7554/eLife.13024.013
DOI:
10.7554/eLife.13024.014
DOI:
10.7554/eLife.13024.021
DOI:
10.7554/eLife.13024.022
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
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