Psoriasis is a chronic autoimmune skin disease with a significant impact on quality of life and potential for severe comorbidities. Inflammation in the skin is induced by immune cells that overexpress pro-inflammatory cytokines, with the Th17 cell playing a crucial role. NLRP3 inflammasome activation is associated with inflammatory diseases and abnormal T cell differentiation. 3H-1,2-dithiole-3-thione (D3T), isolated from cruciferous vegetables, has anti-inflammatory effects and inhibits Th17 differentiation. This study aimed to investigate how D3T reduces skin inflammation and modulates Th17 cell differentiation by inhibiting NLRP3 inflammasome activation. In an imiquimod-induced psoriasis mouse model, D3T treatment demonstrated significant reductions in ear thickness, skin redness, and scaling compared to a control group. Our study also observed decreased expression of ki-67, NLRP3 inflammasome, and cleaved caspase-1 in skin samples, reduced levels of IL-6 and IL-17A in serum samples, and inhibition of Th17 differentiation after D3T application. D3T could also inhibit the expression of NLRP3, caspase-1, and IL-1β in TNF-α stimulated HaCaT cells. The mechanical study also revealed that D3T could inhibit NLRP3 inflammasome activation by inhibiting the JNK pathway in HaCaT cells. These results indicate that targeting NLRP3 inflammasome activation is a promising strategy in the treatment of psoriasis.

Psoriasis is a predominantly Th17 cell-driven chronic autoinflammatory skin disorder. Brevilin A, a natural sesquiterpene lactone extracted from Centipeda minima, has been used as a traditional oriental medicine for allergic diseases for centuries. However, the effects of brevilin A on psoriasis have yet to be established. In this study, we investigated brevilin A to elucidate its potential effects on T cell activities in psoriasis, in animal models and patients. An imiquimod (IMQ)-induced psoriasis-like dermatitis murine model was utilized. Experimental mice were administered different doses of brevilin A (5, 10, 20 mg/kg respectively) for a duration of 5 days. Cutaneous manifestations were measured daily. Under hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC), acanthosis and proinflammatory cytokine expression in the dorsal skin of mice were detected. Enzyme-linked immunosorbent assay (ELISA) was used for the measurement of IL-17A levels in serum samples. Naïve CD4+ T cells, isolated from mice spleen and lymph nodes and from peripheral blood mononuclear cells (PBMCs) of psoriatic patients, were used to evaluate the effects of brevilin A on Th17 differentiation. In brevilin A-treated mice, brevilin A significantly reduced skin redness and scaling; acanthosis as well as IL-6, IL-17A, and ki-67 expressions were downregulated in the dorsal skin, and serum levels of IL-17A were lowered. Brevilin A also inhibited Th17 differentiation. In conclusion, brevilin A demonstrated significant capability in ameliorating skin inflammation in IMQ-induced psoriasis-like dermatitis and could modulate Th17 differentiation. Therefore, brevilin A is potentially pharmacologically effective in the treatment of psoriasis.

The journal retracts the article “Brevilin A Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis and Reduces Th17 Differentiation in Psoriasis Patients”