A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist

被引:185
作者
Xu, WF [1 ]
Presnell, SR [1 ]
Parrish-Novak, J [1 ]
Kindsvogel, W [1 ]
Jaspers, S [1 ]
Chen, Z [1 ]
Dillon, SR [1 ]
Gao, Z [1 ]
Gilbert, T [1 ]
Madden, K [1 ]
Schlutsmeyer, S [1 ]
Yao, L [1 ]
Whitmore, TE [1 ]
Chandrasekher, Y [1 ]
Grant, FJ [1 ]
Maurer, M [1 ]
Jelinek, L [1 ]
Storey, H [1 ]
Brender, T [1 ]
Hammond, A [1 ]
Topouzis, S [1 ]
Clegg, CH [1 ]
Foster, DC [1 ]
机构
[1] Zymogenet Inc, Seattle, WA USA
关键词
D O I
10.1073/pnas.171303198
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-20R alpha and IFN-gamma R1 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.
引用
收藏
页码:9511 / 9516
页数:6
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