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

Kimiko Kuroki, Kaoru Hirose, Yuki Okabe, Yuko Fukunaga, Ami Takahashi, Mitsunori Shiroishi, Mizuho Kajikawa, Shigekazu Tabata, Seiko Nakamura, Toshiyuki Takai, Satoru Koyanagi, Shigehiro Ohdo, Katsumi Maenaka

研究成果: Article

21 引用 (Scopus)

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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.

元の言語English
ページ(範囲)433-438
ページ数6
ジャーナルHuman Immunology
74
発行部数4
DOI
出版物ステータスPublished - 2013 4 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kuroki, K., Hirose, K., Okabe, Y., Fukunaga, Y., Takahashi, A., Shiroishi, M., Kajikawa, M., Tabata, S., Nakamura, S., Takai, T., Koyanagi, S., Ohdo, S., & Maenaka, K. (2013). The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis. Human Immunology, 74(4), 433-438. https://doi.org/10.1016/j.humimm.2012.11.060