Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair

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

Abstract

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. © 2014 The Society for Investigative Dermatology.

Citation

Campbell, L., Emmerson, E., Williams, H., Saville, C. R., Krust, A., Chambon, P., Mace, K. A., & Hardman, M. J. (2014). Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair. Journal of Investigative Dermatology, 134(9), 2447-2457. https://doi.org/10.1038/jid.2014.175

• Journal Article Type: Article
• Acceptance Date: Mar 11, 2014
• Online Publication Date: Apr 9, 2014
• Publication Date: 2014-09
• Deposit Date: Feb 25, 2021
• Journal: Journal of Investigative Dermatology
• Print ISSN: 0022-202x
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 134
• Issue: 9
• Pages: 2447-2457
• DOI: https://doi.org/10.1038/jid.2014.175
• Public URL: https://hull-repository.worktribe.com/output/3587416