Cloning and characterization of IL-22 binding protein, a natural antagonist of IL-10-related T cell-derived inducible factor/IL-22

The class II cytokine receptor family includes the receptors for IFN-alpha beta, IFN-gamma, IL-10, and IL-10-related T cell-derived inducible ractor/I L-22. By screening genomic DNA databases, we identified a gene encoding a p rotein of 231 aa, showing 33 and 34% amino acid identity with the extracell ular domains of the IL-22 receptor and of the IL-20R/eytokine receptor fami ly 2-8, respectively, but lacking the transmembrane and cytoplasmic domains . A lower but significant sequence identity was found with other members of this family such as the IL-10R (29%), cytokine receptor family 2-4/IL-10R beta (30%), tissue factor (26%), and the four IFN receptor chains (23-25%). This gene is located on chromosome 6q24, at 35 kb from the IFNGR1 gene, an d is expressed in various tissues with maximal expression in breast, lungs, and colon. The recombinant protein was found to bind IL-10-related T cell- derived inducible factor/IL-22, and to inhibit the activity of this cytokin e on hepatocytes and intestinal epithelial cells. We propose to name this n atural cytokine antagonist IL-22BP for IL-22 binding protein.