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The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis

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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
CIA mice
avidity effect
Issue Date: Apr-2013
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)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 黒木 喜美子

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