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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)433-438
Number of pages6
JournalHuman Immunology
Volume74
Issue number4
DOIs
Publication statusPublished - Apr 1 2013

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HLA-G Antigens
Experimental Arthritis
Immunosuppressive Agents
Disulfides
Foot Joints
Double-Blind Method
Placenta
Immune System
Rheumatoid Arthritis
Anti-Inflammatory Agents
Mothers
Pregnancy

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kuroki, K., Hirose, K., Okabe, Y., Fukunaga, Y., Takahashi, A., Shiroishi, M., ... 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

The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis. / Kuroki, Kimiko; Hirose, Kaoru; Okabe, Yuki; Fukunaga, Yuko; Takahashi, Ami; Shiroishi, Mitsunori; Kajikawa, Mizuho; Tabata, Shigekazu; Nakamura, Seiko; Takai, Toshiyuki; Koyanagi, Satoru; Ohdo, Shigehiro; Maenaka, Katsumi.

In: Human Immunology, Vol. 74, No. 4, 01.04.2013, p. 433-438.

Research output: Contribution to journalArticle

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, vol. 74, no. 4, pp. 433-438. https://doi.org/10.1016/j.humimm.2012.11.060
Kuroki, Kimiko ; Hirose, Kaoru ; Okabe, Yuki ; Fukunaga, Yuko ; Takahashi, Ami ; Shiroishi, Mitsunori ; Kajikawa, Mizuho ; Tabata, Shigekazu ; Nakamura, Seiko ; Takai, Toshiyuki ; Koyanagi, Satoru ; Ohdo, Shigehiro ; Maenaka, Katsumi. / The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis. In: Human Immunology. 2013 ; Vol. 74, No. 4. pp. 433-438.
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