LiangxueJiedu Formula improves psoriatic dermatitis by regulating the circadian clock to inhibit IL-17-producing Th17 and γδT cells

Abstract

Abstract Background Psoriasis is an immune-mediated inflammatory skin disease. The circadian clock influence immune cells and control the skin’s inflammatory response. In this study, we observed the effect of LiangxueJiedu Formula (LXJDF) on imiquimod-induced per2-knockout mice to explore the mechanism of Chinese medicinal herbs in improving skin inflammation via the circadian clock. Methods The per2−/− mice were randomly divided into the model group, the LXJDF group, and the positive drug group (dexamethasone). The dorsal skin of mice was smeared with imiquimod at 9:00 AM (ZT1), and the corresponding drugs were given at 10:00AM (ZT2) and 10:00 PM (ZT14), respectively. The wild-type (WT) mice were smeared vaseline as the control group. The skin lesions were observed and PASI was performed for six consecutive days. The pathological morphology of the skin was determined by HE and immunofluorescence (Ki67, loricrin, and IL-17A) staining, and the epidermis thickness was measured. The spleen weight and index were calculated, and the splenocyte subtypes and serum cytokine levels were detected by flow cytometry. The serum melatonin levels were detected by ELISA. The gene expressions of inflammatory cytokines in the skin were determined by qPCR. The gene and protein expressions of circadian clock-related genes (CLOCK, BMAL1, REV-ERBα, NFIL3, and RORγt) in the skin were determined by qPCR and western blot. Results LXJDF could significantly improve the psoriasiform skin lesions, including the reduction of PASI, thinning of epidermal thickness, inhibition of keratinocytes proliferation, and parakeratosis at two-time points (ZT2 and ZT14). LXJDF could reduce the spleen weight and index and inhibit the number of Th17 cells, γδT cells, and the serum inflammatory factors levels of IL-17A, IL-17F, TNF-α, IL-22, IL-6. In addition, LXJDF could significantly down-regulate the mRNA expressions of IL-17A, IL-17F, IL-23, and IL-6 in the skin. LXJDF significantly increased the expressions of BMAL1 and REV-ERBα, and decreased NFIL3 and RORγt. Conclusions LXJDF ameliorates psoriatic dermatitis by regulating the circadian clock to inhibit IL-17-producing Th17 and γδT cells.