Comparison of interleukin-22 and interleukin-10 soluble receptor complexes

Academic Article

Abstract

  • Interleukin-22 (IL-22) is a cellular homolog of IL-10 that stimulates the production of acute-phase reactants. IL-22 and IL-10 require different ligand-specific receptor chains (IL-22R and IL-10R1) but share a second receptor chain (IL-10R2) to initiate cellular responses. The quaternary structures and the ability of IL-22 and IL-10 to engage soluble (s) IL-10R1, IL-22R, IL-10R2 receptor chains were analyzed using size exclusion chromatography and surface plasmon resonance techniques. In contrast to IL-10, which is a homodimer, IL-22 is a monomer in solution that forms a 1:1 interaction with sIL-22R. Kinetic binding data reveal sIL-22R and sIL-10R1 exhibit specific nanomolar binding constants for IL-22 (kon/koff = 14.9 nM) and a monomeric isomer of IL-10 (IL-10M1) (kon/koff = 0.7 nM), respectively. In contrast, IL-10R2 exhibits essentially no affinity for IL-22 (Keq ∼ 1 mM) or IL-10M1 (Keq ∼ 2 mM) alone but displays a substantial increase in affinity for the IL-10/sIL-10R1 (Keq ∼ 350 μM) and IL-22/sIL-22R (Keq ∼ 45 μM) complexes. Three-dimensional models of IL-22 and IL-10 receptor complexes suggest two receptor residues (Gly-44 and Arg-96) are largely responsible for the marked differences in ligand affinity observed for sIL-10R1 and sIL-22R vs. sIL-10R2.
  • Digital Object Identifier (doi)

    Author List

  • Logsdon NJ; Jones BC; Josephson K; Cook J; Walter MR
  • Start Page

  • 1099
  • End Page

  • 1112
  • Volume

  • 22
  • Issue

  • 11