Interleukin (IL)-22, discovered in 2000, is a member of the IL-10 family of cytokines. The major sources of IL-22 are activated T1- and NK-cells. IL-22 acts via a heterodimeric receptor complex consisting of IL-22R1 and IL-10R2. Neither resting nor activated immune cells express IL-22R1 or respond to IL-22. In contrast, tissue cells at outer body barriers, i.e. of the skin, kidney, and the digestive and respiratory systems are targets of this cytokine. IL-22 functions by promoting the anti-microbial defense, protecting against damage, and re-organizing non-immune tissues. Furthermore, IL-22 induces acute phase reactants. These findings indicate that IL-22 represents a novel type of immune mediator that, although produced by immune cells, regulates tissue protection and homeostasis.