Abstract
We report the identification of a novel human cytokine, distantly related to interleukin (IL)-10, which we term IL-22. IL-22 is produced by activated T cells. IL-22 is a ligand for CRF2-4, a member of the class II cytokine receptor family. No high affinity ligand has yet been reported for this receptor, although it has been reported to serve as a second component in IL-10 signaling. A new member of the interferon receptor family, which we term IL-22R, functions as a second component together with CRF2-4 to enable IL-22 signaling. IL-22 does not bind the IL-10R. Cell lines were identified that respond to IL-22 by activation of STATs 1, 3, and 5, but were unresponsive to IL-10. In contrast to IL-10, IL-22 does not inhibit the production of proinflammatory cytokines by monocytes in response to LPS nor does it impact IL-10 function on monocytes, but it has modest inhibitory effects on IL-4 production from Th2 T cells.
MeSH terms
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Amino Acid Sequence
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Blotting, Western
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Cell Line
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DNA-Binding Proteins / metabolism
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Electrophoresis, Polyacrylamide Gel
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Enzyme Activation
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Enzyme-Linked Immunosorbent Assay
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Expressed Sequence Tags
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Flow Cytometry
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Humans
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Interleukin-10 / metabolism
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Interleukin-10 Receptor beta Subunit
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Interleukin-22
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Interleukins / chemistry*
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Interleukins / metabolism*
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Ligands
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins*
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Molecular Sequence Data
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Monocytes / metabolism
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Protein Binding
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Receptors, Cytokine / metabolism*
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Receptors, Interleukin / metabolism*
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Receptors, Interleukin-10
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Sequence Homology, Amino Acid
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Signal Transduction*
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T-Lymphocytes / metabolism
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Th2 Cells / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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DNA-Binding Proteins
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IL10RB protein, human
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Interleukin-10 Receptor beta Subunit
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Interleukins
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Ligands
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, Cytokine
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Receptors, Interleukin
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Receptors, Interleukin-10
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Tumor Necrosis Factor-alpha
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interleukin-22 receptor
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Interleukin-10
Associated data
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GENBANK/AF279437
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GENBANK/AF286095