The activation and regulation of IL-17 receptor mediated signaling

Interleukin-17 (IL-17), the signature cytokine produced by T helper 17 (Th17) cells, plays pivotal roles in host defense responses against microbial invasion, as well as in the pathogenesis of autoimmune diseases and allergic syndromes. IL-17 activates several downstream signaling pathways including NF-κB, MAPKs and C/EBPs to induce gene expression of antibacterial peptides, proinflammatory chemokines and cytokines and matrix metalloproteinases (MMPs). IL-17 can also stabilize mRNAs of genes induced by TNFα. Although the physiological and pathological functions of IL-17 have been studied for many years, the landscape of its signaling transduction has not been described until recently. The cytosolic adaptor molecule Act1 (also known as CIKS) is considered as the master mediator of IL-17 signaling. In this review, we will summarize recent progress on activation and regulation of IL-17 mediated signal transduction, especially on Act1 mediated regulation of the signaling.

•Act1 mediated activation of IL-17 signaling.•Negative regulation of Act1 mediated IL-17 signaling.•Act1 in IL-17 associated autoimmunity.