title: A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist.
abstract: IL-22 is an IL-10 homologue that binds to and signals through the class II cytokine receptor heterodimer IL-22RA1/CRF2-4. IL-22 is produced by T cells and induces the production of acute-phase reactants in vitro and in vivo, suggesting its involvement in inflammation. Here we report the identification of a class II cytokine receptor designated IL-22RA2 (IL-22 receptor-alpha 2) that appears to be a naturally expressed soluble receptor. IL-22RA2 shares amino acid sequence homology with IL-22RA1 (also known as IL-22R, zcytor11, and CRF2-9) and is physically adjacent to IL-20Ralpha and IFN-gammaR1 on chromosome 6q23.3-24.2. We demonstrate that IL-22RA2 binds specifically to IL-22 and neutralizes IL-22-induced proliferation of BaF3 cells expressing IL-22 receptor subunits. IL-22RA2 mRNA is highly expressed in placenta and spleen by Northern blotting. PCR analysis using RNA from various tissues and cell lines showed that IL-22RA2 was expressed in a range of tissues, including those in the digestive, female reproductive, and immune systems. In situ hybridization revealed the dominant cell types expressing IL-22RA2 were mononuclear cells and epithelium. Because IL-22 induces the expression of acute phase reactants, IL-22RA2 may play an important role as an IL-22 antagonist in the regulation of inflammatory responses.
authors.affiliation: ZymoGenetics Inc., Seattle, WA 98102, USA.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: S R
authors.initials: SR
authors.lastname: Presnell
authors.forename: J
authors.initials: J
authors.lastname: Parrish-Novak
authors.forename: W
authors.initials: W
authors.lastname: Kindsvogel
authors.forename: S
authors.initials: S
authors.lastname: Jaspers
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: S R
authors.initials: SR
authors.lastname: Dillon
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.forename: T
authors.initials: T
authors.lastname: Gilbert
authors.forename: K
authors.initials: K
authors.lastname: Madden
authors.forename: S
authors.initials: S
authors.lastname: Schlutsmeyer
authors.forename: L
authors.initials: L
authors.lastname: Yao
authors.forename: T E
authors.initials: TE
authors.lastname: Whitmore
authors.forename: Y
authors.initials: Y
authors.lastname: Chandrasekher
authors.forename: F J
authors.initials: FJ
authors.lastname: Grant
authors.forename: M
authors.initials: M
authors.lastname: Maurer
authors.forename: L
authors.initials: L
authors.lastname: Jelinek
authors.forename: H
authors.initials: H
authors.lastname: Storey
authors.forename: T
authors.initials: T
authors.lastname: Brender
authors.forename: A
authors.initials: A
authors.lastname: Hammond
authors.forename: S
authors.initials: S
authors.lastname: Topouzis
authors.forename: C H
authors.initials: CH
authors.lastname: Clegg
authors.forename: D C
authors.initials: DC
authors.lastname: Foster
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D015152:Blotting, Northern; D002277:Carcinoma / Q000378:metabolism; D002460:Cell Line; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005796:Genes; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007378:Interleukins / Q000037:antagonists & inhibitors*; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009928:Organ Specificity; D010051:Ovarian Neoplasms / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D021101:Radiation Hybrid Mapping; D018123:Receptors, Interleukin / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014162:Transfection; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D000097043:Interleukin-22; C415369:interleukin-22 receptor