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

Ami Takahashi; Kimiko Kuroki; Yuki Okabe; Yoshiyuki Kasai; Naoki Matsumoto; Chisato Yamada; Toshiyuki Takai; Toyoyuki Ose; Shigeyuki Kon; Tadashi Matsuda; Katsumi Maenaka

doi:10.1016/j.humimm.2016.01.010

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

Ami Takahashi, Kimiko Kuroki, Yuki Okabe, Yoshiyuki Kasai, Naoki Matsumoto, Chisato Yamada, Toshiyuki Takai, Toyoyuki Ose, Shigeyuki Kon, Tadashi Matsuda, Katsumi Maenaka

IDAC - Division of Aging Science

Hokkaido University

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and β2m-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.

Original language	English
Pages (from-to)	754-759
Number of pages	6
Journal	Human Immunology
Volume	77
Issue number	9
DOIs	https://doi.org/10.1016/j.humimm.2016.01.010
Publication status	Published - 2016 Sept 1

Keywords

CIA mice
HLA-G2
Immunosuppression
LILRB2/ILT4
PIR-B

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10.1016/j.humimm.2016.01.010

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@article{f958f9d17864482ebe7b41afca753d89,

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

abstract = "HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and β2m-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.",

keywords = "CIA mice, HLA-G2, Immunosuppression, LILRB2/ILT4, PIR-B",

author = "Ami Takahashi and Kimiko Kuroki and Yuki Okabe and Yoshiyuki Kasai and Naoki Matsumoto and Chisato Yamada and Toshiyuki Takai and Toyoyuki Ose and Shigeyuki Kon and Tadashi Matsuda and Katsumi Maenaka",

note = "Funding Information: This work was partly supported by MEXT KAKENHI Grant Number 22121007 , JSPS KAKENHI Grant Number 23770102 and 25870019 , Platform for Drug Discovery, Informatics, and Structural Life Science founded by Japan Agency for Medical Research and Development and the Naito foundation. Publisher Copyright: {\textcopyright} 2016 American Society for Histocompatibility and Immunogenetics",

year = "2016",

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day = "1",

doi = "10.1016/j.humimm.2016.01.010",

language = "English",

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T1 - The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice

AU - Takahashi, Ami

AU - Kuroki, Kimiko

AU - Okabe, Yuki

AU - Kasai, Yoshiyuki

AU - Matsumoto, Naoki

AU - Yamada, Chisato

AU - Takai, Toshiyuki

AU - Ose, Toyoyuki

AU - Kon, Shigeyuki

AU - Matsuda, Tadashi

AU - Maenaka, Katsumi

N1 - Funding Information: This work was partly supported by MEXT KAKENHI Grant Number 22121007 , JSPS KAKENHI Grant Number 23770102 and 25870019 , Platform for Drug Discovery, Informatics, and Structural Life Science founded by Japan Agency for Medical Research and Development and the Naito foundation. Publisher Copyright: © 2016 American Society for Histocompatibility and Immunogenetics

PY - 2016/9/1

Y1 - 2016/9/1

N2 - HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and β2m-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.

AB - HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and β2m-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.

KW - CIA mice

KW - HLA-G2

KW - Immunosuppression

KW - LILRB2/ILT4

KW - PIR-B

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DO - 10.1016/j.humimm.2016.01.010

M3 - Article

C2 - 26805457

AN - SCOPUS:84955568221

SN - 0198-8859

VL - 77

SP - 754

EP - 759

JO - Human Immunology

JF - Human Immunology

IS - 9

ER -

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

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Keywords

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