A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist.
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.
Xu
W
W
ZymoGenetics Inc., Seattle, WA 98102, USA.
Presnell
S R
SR
Parrish-Novak
J
J
Kindsvogel
W
W
Jaspers
S
S
Chen
Z
Z
Dillon
S R
SR
Gao
Z
Z
Gilbert
T
T
Madden
K
K
Schlutsmeyer
S
S
Yao
L
L
Whitmore
T E
TE
Chandrasekher
Y
Y
Grant
F J
FJ
Maurer
M
M
Jelinek
L
L
Storey
H
H
Brender
T
T
Hammond
A
A
Topouzis
S
S
Clegg
C H
CH
Foster
D C
DC
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
D007378:Interleukins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D000097043:Interleukin-22; C415369:interleukin-22 receptor