The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice

被引：16

作者：

Takahashi, Ami ^{[1
]}

Kuroki, Kimiko ^{[1
]}

Okabe, Yuki ^{[1
]}

Kasai, Yoshiyuki ^{[1
]}

Matsumoto, Naoki ^{[2
]}

Yamada, Chisato ^{[1
]}

Takai, Toshiyuki ^{[3
]}

Ose, Toyoyuki ^{[1
]}

Kon, Shigeyuki ^{[2
]}

Matsuda, Tadashi ^{[2
]}

Maenaka, Katsumi ^{[1
,4
]}

机构：

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

[2] Hokkaido Univ, Fac Pharmaceut Sci, Dept Immunol, Sapporo, Hokkaido, Japan

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

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

来源：

HUMAN IMMUNOLOGY | 2016年 / 77卷 / 09期

关键词：

HLA-G2; LILRB2/ILT4; PIR-B; CIA mice; Immunosuppression; ANTIGEN-PRESENTING CELLS; CD4(+) T-CELLS; BINDING; INHIBITION; SUPPRESSES; MATURATION; RESPONSES; RECEPTOR; PROTEIN;

D O I：

10.1016/j.humimm.2016.01.010

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 is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and beta 2m-free forms have been identified. The major isoform, HLA-G1 (and its soluble type HLA-G5), binds to the inhibitory immune receptors, leukocyte immunoglobulin (Ig)-like receptor (LILR) B1 and LILRB2. We previously reported that HLA-G1 also binds to paired Ig-like receptor (PIR)-B, a mouse homolog of LILRBs, and had a significant immunosuppressive effect in collagen-induced arthritis (CIA) mice. Although HLA-G2 and its soluble form HLA-G6 bind specifically to LILRB2, its functional characteristics are largely unknown. In this study, we report the significant immunosuppressive effect of HLA-G2 dimer in CIA mice. Surface plasmon resonance analysis revealed a specific interaction of HLA-G2 with PIR-B. CIA mice were administered HLA-G2 protein subcutaneously once in the left footpad and clinical severity was evaluated in a double-blind study. A single administration of HLA-G2 maintained a suppressive effect for over 1 month. These results suggested that the HLA-G2 protein might be a useful biopharmaceutical for the treatment of rheumatoid arthritis by binding to inhibitory PIR-B. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

引用

页码：754 / 759

页数：6

共 23 条

[21] Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G
Shiroishi, M
Tsumoto, K
Amano, K
Shirakihara, Y
Colonna, M
Braud, VM
Allan, DSJ
Makadzange, A
Rowland-Jones, S
Willcox, B
Jones, EY
van der Merwe, PA
Kumagai, I
Maenaka, K
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (15) : 8856 - 8861
[22] Impaired dendritic cell maturation and increased TH2 responses in PIR-B-/- mice
Ujike, A
Takeda, K
Nakamura, A
Ebihara, S
Akiyama, K
Takai, T
[J]. NATURE IMMUNOLOGY, 2002, 3 (06) : 542 - 548
[23] HLA-G1 and HLA-G5 isoforms have an additive effect on NK cytolysis
Zhang, Wei-Qun
Xu, Dan-Ping
Liu, Di
Li, Ying-Ying
Ruan, Yan-Yun
Lin, Aifen
Yan, Wei-Hua
[J]. HUMAN IMMUNOLOGY, 2014, 75 (02) : 182 - 189

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