Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions.

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-1ß, which was reversed by exogenously added estradiol. The suppressive effect of estradiol on the production of IL-1ß and IL-17A was abolished in mice lacking estrogen receptors in neutrophils and macrophages (Esr1f/fEsr2f/fLysM-Cre+ mice). IL-1ß, which is required for production of IL-17A in the psoriasis model, was mainly produced by neutrophils and inflammatory macrophages. Estradiol suppressed IL-1ß 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.

Case of H syndrome with massive skin involvement, retroperitoneal fibrosis and Raynaud's phenomenon with a novel mutation in the SLC29A3 gene.

We describe a case of H syndrome with massive skin involvement, retroperitoneal fibrosis and Raynaud's phenomenon. A 48-year-old man with parents of a consanguineous marriage, first appeared with decreased urine output, skin sclerosis on his inner thighs and short stature (142 cm, 47 kg). The patient had suffered from hearing loss since the age of 1 year, and his secondary sexual characteristics had not developed. Computed tomography showed periaortic fibrosis, bilateral ureteral stenosis, hydronephrosis and sclerosis of the germinal cords. A biopsy from the retroperitoneal mass revealed remarkable fibrosis with chronic inflammatory cells. Biopsies from the skin lesion showed thick collagen bundles through the dermis and lymphohistiocytic infiltration with numerous plasma cells. Serum inflammatory markers, such as C-reactive protein, vascular endothelial factor, transforming growth factor-ß and soluble interleukin-2 receptor, were elevated. Prednisolone was effective in treating skin lesions and in lowering serum inflammatory markers. After a long period of follow up, genomic DNA of the patient was obtained, and we identified a homozygous mutation in exon 5, c.625G>A, which caused transition of glycine to arginine, p.Gly208Arg, in the patient, but not in DNA samples from another 50 healthy individuals. This is the first case of H syndrome with Raynaud's phenomenon and retroperitoneal fibrosis, and the first Japanese case of H syndrome reported in the English published work with a novel mutation in the SLC29A3 gene.