The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis
| Autor: | Yuko Fukunaga, Toshiyuki Takai, Shigekazu Tabata, Kimiko Kuroki, Mizuho Kajikawa, Shigehiro Ohdo, Ami Takahashi, Yuki Okabe, Mitsunori Shiroishi, Seiko Nakamura, Satoru Koyanagi, Kaoru Hirose, Katsumi Maenaka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_treatment Dimer Immunology HLA-G Arthritis CIA mice Severity of Illness Index Injections Arthritis Rheumatoid Mice chemistry.chemical_compound Immune system In vivo Immune Tolerance medicine Animals Immunology and Allergy Avidity Disulfides Receptors Immunologic Receptor Collagen Type II HLA-G Antigens immunosuppression Chemistry Immunosuppression General Medicine medicine.disease Arthritis Experimental Molecular biology avidity effect PIR-B Biochemistry Mice Inbred DBA Joints Protein Multimerization Immunosuppressive Agents Protein Binding |
| Zdroj: | HUMAN IMMUNOLOGY. 74(4):433-438 |
| ISSN: | 0198-8859 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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