IL-22 is a cytokine structurally related to IL-10. Originally identified as a murine gene induced by IL-9 in T and mast cells, IL-22 was initially designated ILTIF (IL-10-related T cell-derived inducible factor). IL-22 belongs to a family of cytokines with limited homology to IL-10, namely IL-10, IL-19, IL-20, IL-24, IL-26, and the IFN-lambdas, IL-28A, IL-28B and IL-29. Human IL-22 shares 79% amino acid identity with murine IL-22 and 25% identity with human IL-10. IL-22 biological activity is initiated by binding to a cell surface complex composed of IL-22R1 and IL-10R2 receptor chains. Activity is further regulated through interactions with the soluble binding protein, IL-22BP, which shares sequence similarity with an extracellular region of IL-22R1 (sIL-22R1). Both chains of the IL-22R complex belong to the class II CRF. Two types of IL-22 binding receptors have been discovered, a membrane-bound receptor and a soluble receptor, both encoded by different genes. IL-22 is produced by Th17 cells and newly identified Th22 cells. It plays a critical role in mucosal immunity in addition to the deregulated inflammation observed in autoimmune diseases.