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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.


Laura Campbell

Elaine Emmerson

Helen Williams

Charis R. Saville

Andrée Krust

Pierre Chambon

Kimberly A. Mace


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.


Campbell, L., Emmerson, E., Williams, H., Saville, C. R., Krust, A., Chambon, P., …Hardman, M. J. (2014). Estrogen receptor-alpha promotes alternative macrophage activation during cutaneous repair. Journal of Investigative Dermatology, 134(9), 2447-2457.

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
Electronic ISSN 1523-1747
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 134
Issue 9
Pages 2447-2457
Public URL