Interleukin-22 in the pathogenesis and potential treatment of liver diseases

Interleukin (IL)-22, a member of the IL-10 cytokine family, plays critical roles in tissue repair and host defense. IL-22 binds to its hetereodimeric receptor (R) composed of IL-22R1 and IL-10R2 and activates downstream signaling, including Signal transducer and activator of transcription 3 (STAT3) pathways. IL-22 promotes the expression of survival genes in a STAT3-dependent manner. IL-22R1 expression is restricted mainly in epithelial cells while IL-10R2 is ubiquitously expressed in almost all cell types. In the liver, IL-22R1 is expressed in hepatocytes, liver progenitor cells, hepatic stellate cells and liver cancer cells. IL-22 protects the liver in various liver damage models and promotes liver regeneration after liver injury. IL-22 also helps to resolve liver fibrosis by inducing hepatic stellate cell senescence. IL-22 is considered a pro-inflammatory cytokine in viral hepatitis although it does not directly act on immune cells. IL-22 is reported to be involved in the development of liver cancer and in regulating energy metabolism. Studies on IL-22 in liver inflammation, injury and repair will provide valuable information to clarify IL-22 as a potential candidate for treating liver injury and fibrosis.