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 sec...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-01, Vol.276 (4), p.2725-2732
Main Authors: Kotenko, S V, Izotova, L S, Mirochnitchenko, O V, Esterova, E, Dickensheets, H, Donnelly, R P, Pestka, S
Format: Article
Language:English
Subjects:
Amino Acid Sequence
CRF2-9 gene
Cross-Linking Reagents
cytokine receptors
Cytokines - metabolism
g-Interferon receptors
Humans
IL-TIF protein
interleukin 10 receptors
interleukin 22 receptors
Interleukin-22
Interleukins - metabolism
Ligands
Models, Biological
Molecular Sequence Data
Protein Binding
Receptors, Interleukin - isolation & purification
Receptors, Interleukin-10
Signal Transduction
Stat protein
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M007837200