The adaptor protein CIKS/Act1 is essential for imiquimod-induced psoriasis. (171.25)

Abstract Psoriasis is a relapsing skin disease characterized by abnormal keratinocyte proliferation and differentiation and by an influx of inflammatory immune cells. The IL-23/IL-17 cytokines axis is thought to play an important role in the pathogenesis of psoriasis. The TLR7/8 ligand Imiquimod (IMQ) can induce/exacerbate psoriasis in patients and it induces a psoriasis-like condition in mice. In addition to IL-17A and IL-17F, which are produced primarily by Th17 and innate T cells, IL-17C has very recently been implicated in IMQ-induced psoriasis as well. To determine by what mechanisms IL-17 cytokines critically contribute to IMQ-induced psoriasis, we have begun to investigate a mouse model in which signaling by all IL-17 cytokines is abrogated due to the loss of the obligate adaptor protein CIKS/Act1. Importantly, the gene for this adaptor protein has also recently been identified as a strong susceptibility locus in psoriasis. Here we show that IMQ applications induced many markers of psoriasis in wild-type mice, but failed to do so in CIKS-deficient mice. These data demonstrate that signaling by IL-17 cytokines via the adaptor protein CIKS is essential for IMQ-induced psoriasis and thus the CIKS pathway may provide targets for therapeutic intervention in psoriasis. We will report on the progress in understanding the functions of IL-17 cytokines in development of psoriasis.