Summary: The female hormone estradiol helps suppress the itching associated with psoriasis. The results shed light on why men are more susceptible to psoriasis and offer hope for a new targeted treatment for itching disorders.
Source: University of Kyoto
One of the many reasons men envy women, at least when it comes to skin infections, is that women are significantly less likely to develop severe psoriasis. However, the underlying reason for the gender differences was unclear.
Now a team of researchers has found that the female hormone estradiol suppresses psoriasis, and the hormone’s protective role has laid a foundation 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 Tetsuya Honda of the Hamamatsu University School of Medicine, formerly at Kyoto University.
The team tested conditional knockout mice, or Cko mice, that had their ovaries removed but supplemented with estradiol pellets or a placebo. In contrast to wild-type mice, the cko mice without the natural ovarian hormone estradiol showed symptoms of severe skin inflammation.
Once estradiol was administered to these mice, the production of IL-17A and IL-1β cytokines in neutrophil and macrophage immune cells was reversed, thereby reducing 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 rendered estradiol ineffective against the cytokines.
“These results indicate that estradiol suppresses psoriatic inflammation by regulating neutrophil and macrophage cells,” the author concludes.
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Author: press office
Source: University of Kyoto
Contact: Press Office – Kyoto University
Picture: The image is attributed to Kyoto University
Original research: Closed access.
“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 axis. The prevalence and severity of psoriasis is higher in men than 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 and conditional knockout mice were ovariectomized, supplemented with placebo or estradiol pellets, and treated with an imiquimod-containing cream.
Mice lacking endogenous ovarian hormones showed 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 reversed in mice lacking estrogen receptors in neutrophils and macrophages (Ezr1f/fEzr2f/fLysM-Cre+ mice). IL-1β, which is required for the production of IL-17A in the psoriasis model, was mainly produced by neutrophils and inflammatory macrophages. Estradiol suppressed IL-1β production by both neutrophils and macrophages in mice in vivo and in vitro and from human neutrophils in vitro.
Our results suggest a novel mechanism for sex-related differences in clinical psoriatic phenotypes, which may shed new light on psoriatic pathology.