Interplay between IL-22 and IL-22BP in regulating liver fibrosis. IL-22, which is produced by immune cells, targets hepatocytes and HSCs by binding to IL-22R1 and IL-10R2. The well-documented hepatoprotective and antifibrotic effects of IL-22 are mediated by the promotion of hepatocyte survival and induction of HSC senescence, respectively. IL-22BP, which lacks both transmembrane and intracellular domains, binds to IL-22 with a 20- to 1,000-fold higher binding affinity than IL-22R1 and subsequently blocks IL-22 activity, thereby exacerbating liver fibrogenesis.