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Molecular characteristics of rhesus macaque interleukin‐22: cloning, in vitro expression and biological activities
Author(s) -
Yu Lei,
Wang FengJie,
Cui YanFang,
Li Dong,
Yao WenRong,
Yang GuiBo
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12914
Subject(s) - rhesus macaque , biology , macaque , microbiology and biotechnology , exon , gene , immunology , genetics , paleontology
Summary Interleukin‐22 (IL‐22) is a potential therapeutic agent for diseases driven by epithelial injury. To characterize the IL‐22 expressed by rhesus macaques, animals that are irreplaceable for human disease research, rhesus macaque IL‐22 ( rhIL‐22 ) was cloned and expressed, and its biological activity and in vivo distribution were examined. It was found that the rhIL‐22 gene consists of five introns and six exons, including a short non‐coding exon starting 22 bp downstream of a putative TATA box. The amino acid sequence of rhIL‐22 showed 95·5% identity to that of humans, and it shared two conserved disulphide bonds, three N‐glycosylation sites and all the critical residues for binding to IL‐22R1. High levels of IL‐22 mRNA were observed in the liver, pancreas, lymphoid tissues and especially in the outer‐body barriers such as the intestinal tract of rhesus macaques. Functionally, purified rhIL‐22 has a similar but a little earlier effect on signal transducer and activator of transcription 3 phosphorylation at Tyr705 compared with that of commercial human IL‐22. The expression of the antibacterial proteins β‐defensin‐2, S100A8, S100A9, RegIIIα and Muc1 by HT‐29 cells was largely upregulated after stimulation with rhIL‐22. Recombinant rhIL‐22 could also significantly promote the proliferation of human intestinal epithelial cells without affecting cell apoptosis. These data indicate that rhesus macaque IL‐22 is highly similar to that of humans in both structure and function, and tests of therapeutic effects of human IL‐22 on human diseases in rhesus macaques are warranted.