TAOK1 Negatively Regulates IL-17-mediated Signaling And Inflammatory Responses

Interleukin 17(IL-17)is a cytokine which plays important roles in inflammation and is involved in the pathogenesis of numerous autoimmune diseases.However,the regulation of its signaling transduction has not been well described.In this study,we report that thousand and one kinase 1(TAOK1)functions as a negative regulator of IL-17-mediated signal transduction and inflammation.TAOK1 knockdown promotes the IL-17-induced cytokines and chemokines expression and the activation of mitogen-activated protein kinases(MAPKs)and NF-κB p65.We demonstrate that TAOK1 interacts with IL-17RA independent of its kinase activity,and TAOK1 dose dependently prevents the formation of IL-17R-Actl complex.Consistent with this,TAOK1 deficiency exacerbates 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced experimental model of inflammatory bowel disease(IBD)likely by its promotion of IL-17-mediated signaling pathway.TAOK1 expression is decreased in the colons of ulcerative colitis(UC)patients.In conclusion,these findings suggest that TAOK1 is involved in the development of IL-17 related autoimmune disorders.