Study on molecular mechanism of collagen-induced arthritis in cynomolgus monkeys

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03148
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Tokai University
• Principal Investigator: Shiina Takashi 東海大学, 医学部, 教授 (00317744)
• Co-Investigator(Kenkyū-buntansha): 伊藤 靖 滋賀医科大学, 医学部, 教授 (90324566) ; 石垣 宏仁 滋賀医科大学, 医学部, 准教授 (90432301)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: カニクイザル / 疾患モデル / MHC / 関節リウマチ / コラーゲン誘導関節炎

Outline of Final Research Achievements

The development of a collagen-induced arthritis model (CIA) using cynomolgus macaques has been reported about 30 years ago, but its association with major histocompatibility complex (MHC) polymorphism has not been investigated in detail. In this study, we elucidated the molecular mechanism of the CIA onset in the macaques using genetic, immunological and pathological techniques. We identified a CIA-susceptible MHC class II allele by DNA typing of the MHC genes and revealed that the allele has the identical amino acid motif sequence as rheumatoid arthritis-sensitive human leukocyte antigen (HLA) alleles. Furthermore, individuals that have the MHC allele suggested to be produced a large amount of type II collagen-specific Th1 type IgG1 antibody and more strongly induced inflammation of CIA.

Free Research Field

免疫遺伝学

Academic Significance and Societal Importance of the Research Achievements

本課題により長年に渡り不明であったCIAと感受性を示すMHC多型が同定され、関節リウマチと類似した遺伝学および免疫学特徴が見出された点に学術的意義があり、他のHLA関連疾患モデルの作出のための貴重な基礎的データを取得できたと考えられる。このMHC多型に基づくCIAモデルの作出から、個体数削減と再現性を重視した非臨床試験への展開、関節リウマチの治療法開発に関する斬新なシーズの創生等が将来的に期待される。