Study on molecular mechanism of collagen-induced arthritis in cynomolgus monkeys
| Project/Area Number |
19H03148
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 42040:Laboratory animal science-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| 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 / リウマチ / 自己免疫疾患 |
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| Outline of Research at the Start |
申請者らは、これまでに5,500頭に及ぶDNA検査から多数のMHC統御ザルを検出した。この次段階として、MHC多型に基づく疾患解析を実施し、その成果を治療法の開発に繋げることが重要課題の一つである。本課題では、RAモデルであるCIAを例として、CIA発症の分子機序を解明することを目的とする。具体的には、遺伝学、免疫学および病理学の多面的な解析から、CIAと関連するMHC多型、CIAの重症度を規定する多型マーカーやバイオマーカーの同定等、CIA発症と関連する遺伝要因を明らかにする。個体数削減と再現性を重視した非臨床試験の実施やCIAとRAとの解析データを対比させながら進める点に独創性がある。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] No Tumorigenicity of Allogeneic Induced Pluripotent Stem Cells in Major Histocompatibility Complex-matched Cynomolgus Macaques.2021
Author(s)
Ishigaki H, Pham VL, Terai J, Sasamura T, Nguyen CT, Ishida H, Okahara J, Kaneko S, Shiina T, Nakayama M, Itoh Y, Ogasawara K.
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Journal Title
Cell Transplantation
Volume: Jan-Dec;30
Pages: 963689721992066-963689721992066
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Low replicative fitness of neuraminidase inhibitor-resistant H7N9 avian influenza A virus with R292K substitution in neuraminidase in cynomolgus macaques compared with I222T substitution.2020
Author(s)
Suzuki S, Shichinohe S, Itoh Y, Nakayama M, Ishigaki H, Mori Y, Ogata-Nakahara A, Nguyen TC, Okamatsu M, Sakoda Y, Kida H, Ogasawara K.
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Journal Title
Antiviral Research
Volume: 178
Pages: 104790-104790
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Histological analysis of fundic gland polyps enlarged by proton pump inhibitors2019
Author(s)
Fukuda M, Ishigaki H, Sugimoto M, Mukaisho K, Matsubara A, Ishida H, Moritani S, Itoh Y, Sugihara H, Andoh A, Ogasawara K, Murakami K, Kushima R
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Journal Title
Histopathology
Volume: 75
Issue: 4
Pages: 537-545
DOI
Related Report
Peer Reviewed
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[Journal Article] Inactivated whole virus particle vaccine with potent immunogenicity and limited IL-6 production is ideal for influenza2019
Author(s)
Sekiya T, Mifsud EJ, Ohno M, Nomura N, Sasada M, Fujikura D, Daito T, Shingai M, Ohara Y, Nishimura T, Endo M, Mitsumata R, Ikeda T, Hatanaka H, Kitayama H, Motokawa K, Sobue T, Suzuki S, Itoh Y, Brown LE, Ogasawara K, Kino Y, Kida H
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Journal Title
Vaccine
Volume: 37
Issue: 15
Pages: 2158-2166
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cynomolgus macaque IL37 polymorphism and control of SIV infection2019
Author(s)
Shiina Takashi、Suzuki Shingo、Congy-Jolivet Nicolas、Aarnink Alice、Garchon Henri-Jean、Dereuddre-Bosquet Nathalie、Vaslin Bruno、Tchitchek Nicolas、Desjardins Delphine、Autran Brigitte、Lambotte Olivier、Theodorou Ioannis、Le Grand Roger、Blancher Antoine
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 7981-7981
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Nomenclature report 2019: major histocompatibility complex genes and alleles of great and small ape and old and new world monkey species2019
Author(s)
de Groot NG, Otting N, Maccari G, Robinson J, Hammond JA, Blancher A, Lafont BAP, Guethlein LA, Wroblewski EE, Marsh SGE, Shiina T, Walter L, Vigilant L, Parham P, O'Connor DH, Bontrop RE
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Journal Title
Immunogenetics
Volume: 72
Pages: 25-36
Related Report
Peer Reviewed / Int'l Joint Research
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