Isogarcinol,a natural compound extracted fromGarciniamangosanaL.,has a significant immunosuppressive effect on systemic lupus erythematosus and rheumatoid arthritis.Here we demonstrate isogarcinol has thepotentialto ameliorate imiquimodinduced psoriasis-like skin lesions in mice.It strongly attenuates the aberrant proliferation and differentiation of keratinocytes,and also alleviated the infiltration of inflammatory cellsin dermis.More importantly,when compared with vehicle-treated imiquimod-induced mice,gene expressionlevelsof the cytokines involvedIL-23/Th17axiswere significantly inhibited in the dorsal skin lessionsofisogarcinol-treated imiquimod-induced group,so wereIL-6,IL-2 and even interferon(IFN)-γ.Consistent with these,oral gavage of isogarcinol corrected the abnormal constitution of T cells and suppressed the differentiation of CD4+T cells to Th17in spleen induced by imiquimod.Of interest,it elevates the response of CD4+CD25+FoxP+regulatory T cells in spleen and boosts highly IL-10 expression in skin and serum to enhance the inhibition.Moreover,Isogarcinol does less harm to the liver and kidney than cyclosporine A(CsA)for mice,especially to kidney.In vitro,isogarcinol shows a potent inhibition to the cell proliferation and inflammatory protein expression ofLPS-stimulated HaCaT keratinocyte cells.Furthermore,isogarcinol displays a highly specific lethal effect on HCaT instead of Jurkat and RAW264.7 in comparison withCsA.Taken together,we suggest that isogarcinol is a promising immunosuppressive agent for imiquimod-induced psoriasis-like skin lesions in mice.