title: Interleukin (IL)-22, a novel human cytokine that signals through the interferon receptor-related proteins CRF2-4 and IL-22R.
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.
authors.affiliation: Department of Molecular Biology, Genentech, Inc., South San Francisco, California 94080, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Aggarwal
authors.forename: W H
authors.initials: WH
authors.lastname: Ho
authors.forename: J
authors.initials: J
authors.lastname: Foster
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Stinson
authors.forename: W I
authors.initials: WI
authors.lastname: Wood
authors.forename: A D
authors.initials: AD
authors.lastname: Goddard
authors.forename: A L
authors.initials: AL
authors.lastname: Gurney
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D020224:Expressed Sequence Tags; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D011485:Protein Binding; D018121:Receptors, Cytokine / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D004268:DNA-Binding Proteins; D016753:Interleukin-10; D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; C081846:IL10RB protein, human; C415369:interleukin-22 receptor