LAUSR

BACKGROUND AND PURPOSE The anthelmintic drug praziquantel (PZQ) has been used as a standard treatment for schistosomiasis for over 40 years. This study aimed to repurpose PZQ to treat psoriasis. EXPERIMENTAL APPROACH Psoriasis-like skin inflammation was induced in mice by topical application of imiquimod or intradermal injection of recombinant IL-23. PZQ was either orally or topically administrated during the psoriasis induction period. KEY RESULTS Mice treated with either oral or topical PZQ exhibited markedly improved psoriasiform skin symptoms when compared to control mice, as judged by disease severity score, epidermal thickening, inflammatory cell infiltration, and spleen size. Flow cytometric analysis of infiltrating immune cells from mouse skin displayed reduced infiltration of Th17 cells. In vitro experiments revealed that PZQ inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation and RORγt expression in splenic CD4+ T cells. PZQ also decreased STAT3 phosphorylation in HEK-A/F cells. Downregulation of STAT3 phosphorylation in these cells accounts for the decreased number of Th17 cells and keratinocytes. CONCLUSION AND IMPLICATIONS These results amount to the first preclinical evidence that PZQ may effectively treat psoriasis, and suggest that PZQ alleviates symptoms in mice by inhibiting STAT3 phosphorylation, thereby suppressing Th17 immune responses.