Summary: The female hormone estradiol helps suppress itch associated with psoriasis. The findings shed light on why men are more prone to psoriasis and offers hope for new targeted treatment for itch disorders.
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 sex differences had been unclear.
Now, a team of researchers has found that the female hormone estradiol suppresses psoriasis, and the protective role of the hormone has provided a basis for its therapeutic potential.
“Our results have 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 Hamamatsu University School of Medicine’s Tetsuya Honda, formerly of Kyoto University.
The team tested conditional knockout mice, or cko mice, with ovaries removed but supplemented with estradiol pellets or a placebo. In contrast to wild-type mice, the cko mice without the natural ovarian hormones estradiol showed symptoms of severe skin inflammation.
Once these mice were given estradiol, the production of IL-17A and IL-1β cytokines in neutrophil and macrophage immune cells was reversed, reducing the inflammation. This effect was also observed in human neutrophils in vitro.
What intrigued the researchers was how the lack of estrogen receptors in immune cells made estradiol ineffective against the cytokines.
“These results indicate that estradiol suppresses psoriatic inflammation by regulating neutrophil and macrophage cells,” concludes the author.
Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions
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.
We studied whether estradiol, a female hormone, plays protective roles 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 an imiquimod-containing cream 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 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.
Our results suggest a novel mechanism for sex-dependent differences in psoriasis clinical phenotypes that may shed new light on the pathology of psoriasis.