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 1month. 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.
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Electronic address: k-kimiko@pharm.hokudai.ac.jp.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kuroki
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okabe
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kasai
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Yamada
authors.affiliation: Department of Experimental Immunology, IDAC, Tohoku University, Sendai, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Ose
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.affiliation: Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
authors.affiliation: Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. Electronic address: maenaka@pharm.hokudai.ac.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D019281:Dimerization; D018450:Disease Progression; D059951:HLA-G Antigens / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D000072417:Protein Domains / Q000235:genetics; D015202:Protein Engineering; D011971:Receptors, Immunologic / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D059951:HLA-G Antigens; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic
keywords: CIA mice; HLA-G2; Immunosuppression; LILRB2/ILT4; PIR-B