Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair

Laura Campbell, Elaine Emmerson, Helen Williams, Charis R Saville, Andrée Krust, Pierre Chambon, Kimberly A Mace, Matthew J Hardman

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Efficient local monocyte/macrophage recruitment is critical for tissue repair. Recruited macrophages are polarized toward classical (proinflammatory) or alternative (prohealing) activation in response to cytokines, with tight temporal regulation crucial for efficient wound repair. Estrogen acts as a potent anti-inflammatory regulator of cutaneous healing. However, an understanding of estrogen/estrogen receptor (ER) contribution to macrophage polarization and subsequent local effects on wound healing is lacking. Here we identify, to our knowledge previously unreported, a role whereby estrogen receptor α (ERα) signaling preferentially polarizes macrophages from a range of sources to an alternative phenotype. Cell-specific ER ablation studies confirm an in vivo role for inflammatory cell ERα, but not ERβ, in poor healing associated with an altered cytokine profile and fewer alternatively activated macrophages. Furthermore, we reveal intrinsic changes in ERα-deficient macrophages, which are unable to respond to alternative activation signals in vitro. Collectively, our data reveal that inflammatory cell-expressed ERα promotes alternative macrophage polarization, which is beneficial for timely healing. Given the diverse physiological roles of ERs, these findings will likely be of relevance to many pathologies involving excessive inflammation.

Original languageEnglish
Pages (from-to)2447-2457
Number of pages11
JournalJournal of Investigative Dermatology
Issue number9
Publication statusPublished - Sept 2014

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Macrophages
  • Macrophages, Peritoneal
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide Synthase Type II
  • Ovariectomy
  • Signal Transduction
  • Wound Healing
  • Journal Article
  • Research Support, Non-U.S. Gov't


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