Signaling of interleukin-17 family cytokines in immunity and inflammation

IL-17 cytokine family, though still young since discovery, has recently emerged as critical players in immunity and inflammatory diseases. The prototype cytokine, IL-17A, plays essential roles in promoting inflammation and host defense. IL-17RA, a member of the IL-17 receptor family, forms a complex with another member, IL-17RC, to mediate effective signaling for IL-17A as well as IL-17F, which is most similar to IL-17A, via Act1 and TRAF6 factors. On the other hand, IL-17RA appears to interact with IL-17RB to regulate signaling by another cytokine IL-25. IL-25, the most distant from IL-17A in the IL-17 family, is involved in allergic disease and defense against helminthic parasites. In this review, we discuss recent advancements on signaling mechanisms and biological functions of IL-17A, IL-17F and IL-25, which will shed light on the remaining IL-17 family cytokines and help understand and treat inflammatory diseases.