Summary: Estradiol, a female hormone, helps suppress the itching associated with psoriasis. The findings shed light on why men are more prone to psoriasis and offer hope for a new targeted treatment for itching.
Source: Kyoto University
Among the many reasons men may have for envying women, at least when it comes to skin inflammation, is that women have a significantly lower incidence of severe psoriasis. However, the underlying reason for the gender differences was unclear.
Now, a team of researchers has found that estradiol, a female hormone, suppresses psoriasis, and the hormone’s protective role has provided a basis for its therapeutic potential.
“Our results not only revealed the molecular mechanisms of sex differences in psoriasis, but also shed new light on our understanding of the physiological role of estradiol,” says Tetsuya Honda of the University of Hamamatsu, formerly of Kyoto University.
The team tested conditional knockout mice, or cko mice, with ovaries removed but supplemented with estradiol pellets or a placebo. Unlike wild-type mice, cko mice without the natural ovarian hormones estradiol showed symptoms of severe skin inflammation.
Once these mice were given estradiol, the production of cytokines IL-17A and IL-1β in neutrophil and macrophage immune cells was reversed, reducing inflammation. This effect has also been observed in human neutrophils in vitro.
What intrigued the researchers was how the lack of estrogen receptors in immune cells made estradiol ineffective against cytokines.
“These results indicate that estradiol suppresses psoriatic inflammation by regulating neutrophil and macrophage cells,” concludes the author.
About this neuroscience research news
Author: Press office
Source: Kyoto University
Contact: Press Office – Kyoto University
Image: Image is credited to Kyoto University
Original research: Access closed.
“Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions” by Akimasa Adachi et al. Journal of Allergy and Clinical Immunology
Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
Psoriasis is a common inflammatory skin disease resulting from dysregulation of IL-23/TH17 immune axes. The prevalence and severity of psoriasis are higher in men than in women, although the underlying reasons for this are unclear.
We investigated whether estradiol, a female hormone, plays a protective role in imiquimod-induced psoriatic inflammation in mice by regulating neutrophil and macrophage functions.
Wild-type mice and conditional knockout mice were ovariectomized, supplemented with placebo or estradiol pellets, and cream containing imiquimod was applied.
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 IL-1β and IL-17A production was abolished in mice lacking estrogen receptors in neutrophils and macrophages (Esr1f/fEsr2f/fLysM-Cre+ mouse). IL-1β, required for the 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 live and in vitro and human neutrophils in vitro.
Our results suggest a novel mechanism for sex-dependent differences in clinical psoriasis phenotypes that may shed new light on psoriasis pathology.
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