Cloning and Characterization of IL-22 Binding Protein, a Natural Antagonist of IL-10-Related T Cell-Derived Inducible Factor/IL-22

Abstract

The class II cytokine receptor family includes the receptors for IFN-αβ, IFN-γ, IL-10, and IL-10-related T cell-derived inducible factor/IL-22. By screening genomic DNA databases, we identified a gene encoding a protein of 231 aa, showing 33 and 34% amino acid identity with the extracellular domains of the IL-22 receptor and of the IL-20R/cytokine receptor family 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-10Rβ (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, and 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 cytokine on hepatocytes and intestinal epithelial cells. We propose to name this natural cytokine antagonist IL-22BP for IL-22 binding protein.

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…The protein, lacking the transmembrane and cytoplasmic domains of typical class II cytokine receptors, displays structural homology with the extracellular portion of IL-22R1 [155]. The purified protein migrated as a 35 to 45-kDa band on SDS-PAGE gels, suggesting existence of glycosylation.…”

“…Indeed, bioinformatics analysis predicts five N-glycosylation sites (Asn-X-Thr/Ser) based on the protein amino acid sequence. The recombinant protein binds to and inhibits IL-22 activity in hepatocytes and intestinal epithelial cells [155]. Furthermore, cross-linking experiments revealed that the protein binds IL-22 and prevents the formation of IL-22/IL-22R1/IL-10R2 ternary complex [154].…”

“…In 2001, a gene encoding a protein of 231 amino acid length and sharing 33% amino acid identity with the extracellular domain of IL-22R1 has been identified [154,155]. The protein, lacking the transmembrane and cytoplasmic domains of typical class II cytokine receptors, displays structural homology with the extracellular portion of IL-22R1 [155].…”

“…Furthermore, cross-linking experiments revealed that the protein binds IL-22 and prevents the formation of IL-22/IL-22R1/IL-10R2 ternary complex [154]. This protein was termed IL-22 binding protein (IL-22BP) [154,155].…”

Interleukine 22

“…D'autre part, les effets de l'IL-22 peuvent être neutralisés in vivo grâce à l'expression de son récepteur soluble, l'IL-22 binding protein (IL-22BP). L'IL-22BP est exprimée dans les poumons, la peau, la rate et le côlon [11] [12]. Ces observations ajoutent un niveau de complexité supplémen-taire dans la régulation fonctionnelle de l'IL-22 et pourraient rendre compte des résultats divergents rapportés dans les modèles de greffe allogénique de cellules hématopoïétiques et d'inflammation.…”