IL-17 family: Cytokines, receptors and signaling

• IL-17 is essential for host defense against microbial pathogens.
• IL-17 signaling is tightly controlled at different levels of the signaling cascade.
• Things can go wrong: pathogenic roles of IL-17 in autoimmunity.
• IL-17 contributes to intestinal inflammation and tumorigenesis.
• IL-17E potentiates type 2 allergic responses.

The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A–F, plays crucial roles in host defense against microbial organisms and in the development of inflammatory diseases. Although IL-17A is the signature cytokine produced by T helper 17 (Th17) cells, IL-17A and other IL-17 family cytokines have multiple sources ranging from immune cells to non-immune cells. The IL-17 family signals via their correspondent receptors and activates downstream pathways that include NFκB, MAPKs and C/EBPs to induce the expression of anti-microbial peptides, cytokines and chemokines. The proximal adaptor Act1 is a common mediator during the signaling of all IL-17 cytokines so far and is thus involved in IL-17 mediated host defense and IL-17-driven autoimmune conditions. This review will give an overview and recent updates on the IL-17 family, the activation and regulation of IL-17 signaling as well as diseases associated with this cytokine family.