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The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis
| Title: | The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis |
| Authors: | Kuroki, Kimiko Browse this author →KAKEN DB | | Hirose, Kaoru Browse this author | | Okabe, Yuki Browse this author | | Fukunaga, Yuko Browse this author | | Takahashi, Ami Browse this author | | Shiroishi, Mitsunori Browse this author | | Kajikawa, Mizuho Browse this author | | Tabata, Shigekazu Browse this author | | Nakamura, Seiko Browse this author | | Takai, Toshiyuki Browse this author →KAKEN DB | | Koyanagi, Satoru Browse this author →KAKEN DB | | Ohdo, Shigehiro Browse this author →KAKEN DB | | Maenaka, Katsumi Browse this author →KAKEN DB |
| Keywords: | HLA-G | | PIR-B | | CIA mice | | avidity effect | | immunosuppression |
| Issue Date: | Apr-2013 |
| Publisher: | ELSEVIER SCIENCE INC |
| Journal Title: | HUMAN IMMUNOLOGY |
| Volume: | 74 |
| Issue: | 4 |
| Start Page: | 433 |
| End Page: | 438 |
| Publisher DOI: | 10.1016/j.humimm.2012.11.060 |
| PMID: | 23276819 |
| Abstract: | HLA-G, a natural immunosuppressant present in the human placenta during pregnancy, prevents fetal destruction by the maternal immune system. The immunosuppressive effect of HLA-G is mediated by the immune cell inhibitory receptors, LILRB1 and LILRB2. HLA-G forms disulfide-linked dimers by natural oxidation, and the dimer associates with LILRB1/B2 much more strongly than the monomer. Furthermore, the dimer formation remarkably enhanced the LILRB-mediated signaling. In this report, we studied the in vivo immunosuppressive effect of the HLA-G dimer, using the collagen-induced arthritis model mouse. Mice were treated with the HLA-G monomer or dimer intracutaneously at the left foot joint, once or for 5 days, and the clinical severity was evaluated daily in a double-blind study. The HLA-G monomer and dimer both produced excellent anti-inflammatory effects with a single, local administration. Notably, as compared to the monomer, the dimer exhibited significant immunosuppressive effects at lower concentrations, which persisted for about two months. In accordance with this result, a binding study revealed that the HLA-G dimer binds PIR-B, the mouse homolog of the LILRBs, with higher affinity and avidity than the monomer. The HLA-G dimer is expected to be quite useful as an anti-rheumatoid arthritis agent, in small amounts with minimal side effects. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/52923 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 黒木 喜美子
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