Aim: Indirubin(IR),a kind of bisindole compound,is extracted from the leaves of Indigo naturalis,a traditional Chinese herbal medicine that has been widely used in China to treat inflammatory and autoimmune diseases for years.Psoriasis is a chronic immune-mediated inflammatory skin disease in which γδ T cells play an important role.This study aimed to demonstrate the immunoregulation effect of indirubin in inflammatory process of psoriasis and explore the mechanism further.Methods:Mouse were administered with 12.5,25 and 50 mg/kg indirubin,1mg/kg methotrexate(MTX),or normal saline intragastrically.Keratinocyte proliferation,inflammatory cell infiltration,IL-17 mRNA levels,and JAK3/STAT3 signaling pathway related proteins were examined.Moreover,mouse spleen cells were incubated under γδ T cell polarizing conditions with indirubin(2 μM)and cell viability was tested by CCK-8,γδ T cell differentiation was assessed by flow cytometry,activation of JAK3/STAT3 signaling pathway was detected by Western blotting and IL-17A and IFN-γ expression was investigated by RT-PCR.Results: Indirubin ameliorated keratinocyte proliferation,reduced infiltration of CD3+T cells,γδ T cells,and CD11b in dermis to psoriatic lesions,altered γδ T+ cell and CCR6+γδ T amounts in spleen and lymph node specimens,inhibited IL-17A expression and JAK3/STAT3 signaling in psoriatic lesions.In vitro,indirubin inhibited the IL-17A and IFN-γ expression of isolated γδ T cells,suppressed the JAK3/STAT3 signaling activation,but up-regulated SOCS3 expression in γδT cells.Conclusion: Indirubin alleviates IMQ-induced psoriasis-like inflammation by reducing the infiltration of inflammatory cell and cytokine expression,It may inhibit IL-17+ γδ T cell mediated inflammatory responses via JAK3/STAT3 mediated signaling pathway.Our results indicate that indirubin is a promising drug in the treatment of psoriasis by intervening γδ T cell function.