Human interleukin 22 (IL-22), known as IL-10-related T cell-derived inducible factor (IL-TIF), is a protein of 146 amino acids after cleavage of a putative 33 amino acid signal peptide. It has about 79% and 22% amino acid sequence identity with mouse IL-22 and human IL-10, respectively. It is a member of the IL-10 cytokine family which includes IL-10, IL-19, IL-20, IL-24, and IL-26. IL-22 is produced by activated Th1-type T cells and NK cells and may interact with its receptor as a monomer as evidenced by crystal structure study. The functional IL-22 receptor is of the class 2 subtype and consists of two receptor subunits, IL-22 R (previously an orphan receptor named CRF2-9) and IL-10 Rβ (previously known as CRF2-4). The IL-10 Rβ chain is shared by IL-10, IL-26, IL-28A, IL-28B, and IL-29. IL-22 R is expressed primarily in the pancreas, and to a lesser extent, tissues of the gastrointestinal tract, kidney, and skin. A soluble receptor, IL-22 binding protein (IL-22BP), has also been described and may act as an endogenous inhibitor of IL-22 activity. IL-22 has been shown to activate Jak/STAT and MAPK signaling pathways and upregulate the production of acute phase proteins. Mouse IL-22 expression is induced in various organs upon lipopolysaccharide injection, suggesting that it may be involved in inflammatory responses. In humans, this is supported by the observation that IL-22 is produced by synovial fibroblasts and macrophages of rheumatoid arthritis (RA) patients and is capable of inducing pro-inflammatory responses in RA synovial tissues. In addition, it stimulates the production of pro-inflammatory cytokines and anti-microbial defensins in human keratinocytes. These activities result in epidermal hyperplasia in models of human skin.