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Updated: Sep 22, 2025
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
Akimasa Adachi1, Tetsuya Honda2, Gyohei Egawa3
1Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Dermatology, Tokyo Metropolitan Bokutoh Hospital, Tokyo, Japan.
Background:
Psoriasis is a common inflammatory skin disease resulting from dysregulation of the IL-23/TH17 immune axis. The prevalence and severity of psoriasis is higher in men than in women, although the underlying reasons for this are unclear.
Objective:
We studied whether estradiol, a female hormone, plays protective roles in imiquimod-induced psoriatic inflammation in mice by regulating neutrophil and macrophage functions.
Methods:
Wild-type mice and conditional knockout mice were ovariectomized, supplemented with placebo or estradiol pellets, and an imiquimod-containing cream applied.
Results:
Mice without endogenous ovarian hormones exhibited exacerbated psoriatic inflammation including increased production of IL-17A and IL-1β, which was reversed by exogenously added estradiol. The suppressive effect of estradiol on the production of IL-1β and IL-17A was abolished in mice lacking estrogen receptors in neutrophils and macrophages (Esr1f/fEsr2f/fLysM-Cre+ mice). IL-1β, which is required for production of IL-17A in the psoriasis model, was mainly produced by neutrophils and inflammatory macrophages. Estradiol suppressed IL-1β production from neutrophils and macrophages in mice both in vivo and in vitro and from human neutrophils in vitro.
Conclusion:
Our results suggest a novel mechanism for sex-dependent differences in psoriasis clinical phenotypes that may shed new light on the pathology of psoriasis.
