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

被引：29

作者：

Kuroki, Kimiko ^{[1
]}

Hirose, Kaoru ^{[1
]}

Okabe, Yuki ^{[1
]}

Fukunaga, Yuko ^{[1
]}

Takahashi, Ami ^{[1
]}

Shiroishi, Mitsunori ^{[2
]}

Kajikawa, Mizuho ^{[3
]}

Tabata, Shigekazu ^{[4
]}

Nakamura, Seiko ^{[1
]}

Takai, Toshiyuki ^{[5
]}

Koyanagi, Satoru ^{[6
]}

Ohdo, Shigehiro ^{[6
]}

Maenaka, Katsumi ^{[1
,7
,8
]}

机构：

[1] Hokkaido Univ, Lab Biomol Sci, Fac Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan

[2] Kyushu Univ, Lab Prot Struct Funct & Design, Grad Sch Pharmaceut Sci, Fukuoka 812, Japan

[3] RIKEN Res Ctr Allergy & Immunol, Lab Infect Immun, Yokohama, Kanagawa, Japan

[4] Kyushu Univ, Fac Med Sci, Dept Adv Med Initiat, Fukuoka 812, Japan

[5] Tohoku Univ, IDAC, Dept Expt Immunol, Sendai, Miyagi 980, Japan

[6] Kyushu Univ, Fac Pharmaceut Sci, Div Clin Pharm, Fukuoka 812, Japan

[7] Japan Sci & Technol Agcy, CREST, Saitama, Japan

[8] Hokkaido Univ, Ctr Res & Educ Drug Discovery, Fac Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan

来源：

HUMAN IMMUNOLOGY | 2013年 / 74卷 / 04期

关键词：

INHIBITORY RECEPTOR; G MOLECULE; CELLS;

D O I：

10.1016/j.humimm.2012.11.060

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：433 / 438

页数：6