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Identification of the functional interleukin-22 (IL-22) receptor complex: the IL-10R2 chain (IL-10Rbeta ) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes.

Interleukin-10 (IL-10)-related T cell-derived inducible factor (IL-TIF; provisionally designated IL-22) is a cytokine with limited homology to IL-10. We report here the identification of a functional IL-TIF receptor complex that consists of two receptor chains, the orphan CRF2-9 and IL-10R2, the second chain of the IL-10 receptor complex. Expression of the CRF2-9 chain in monkey COS cells renders them sensitive to IL-TIF. However, in hamster cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional IL-TIF receptor complex. The CRF2-9 chain (or the IL-TIF-R1 chain) is responsible for Stat recruitment. Substitution of the CRF2-9 intracellular domain with the IFN-gammaR1 intracellular domain changes the pattern of IL-TIF-induced Stat activation. The CRF2-9 gene is expressed in normal liver and kidney, suggesting a possible role for IL-TIF in regulating gene expression in these tissues. Each chain, CRF2-9 and IL-10R2, is capable of binding IL-TIF independently and can be cross-linked to the radiolabeled IL-TIF. However, binding of IL-TIF to the receptor complex is greater than binding to either receptor chain alone. Sharing of the common IL-10R2 chain between the IL-10 and IL-TIF receptor complexes is the first such case for receptor complexes with chains belonging to the class II cytokine receptor family, establishing a novel paradigm for IL-10-related ligands similar to the shared use of the gamma common chain (gamma(c)) by several cytokines, including IL-2, IL-4, IL-7, IL-9, and IL-15.

Pubmed ID: 11035029

Authors

  • Kotenko SV
  • Izotova LS
  • Mirochnitchenko OV
  • Esterova E
  • Dickensheets H
  • Donnelly RP
  • Pestka S

Journal

The Journal of biological chemistry

Publication Data

January 26, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: 1P30-CA72720
  • Agency: NIAID NIH HHS, Id: R01-AI36450
  • Agency: NIAID NIH HHS, Id: R01-AI43369
  • Agency: NCI NIH HHS, Id: R01-CA46465

Mesh Terms

  • Amino Acid Sequence
  • Cross-Linking Reagents
  • Cytokines
  • Humans
  • Interleukins
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Protein Binding
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Signal Transduction