Approach to understanding of pathogenesis and invention of new treatments from the results of preliminary genetic studies
| Project/Area Number |
17K09975
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 高安動脈炎 / iPS細胞 / IL-12 / 一塩基多型 / サイトカイン |
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| Outline of Final Research Achievements |
Takayasu arteritis is a rare disease that affects large arteries, and often affects young women. An SNP in IL12B gene region has been found by genome-wide association study of Takayasu arteritis. IL12B gene encodes p40, which is a shared subunit of IL-12 and IL-23. We used peripheral blood mononuclear cells and iPS cells of patients with Takayasu arteritis and healthy controls, and examined the role of IL12B gene in the pathology of Takayasu arteritis. Supernatant p40 concentration was significantly higher in macrophages from patients with risk-type SNPs than in macrophages from patients without risk-type SNPs. Supernatant p40 concentration was higher in the disease-specific iPS cell-derived macrophages than in the control iPS cell-derived macrophages.
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| Academic Significance and Societal Importance of the Research Achievements |
高安動脈炎患者において、発症リスク型SNPの影響によりp40産生能が高くなり、ヘルパーT細胞の活性化を通して、血管炎病態を引き起こしている可能性が示唆された。2015年、著者らはp40を阻害する生物学的製剤ウステキヌマブを高安動脈炎患者3名に投与するパイロット試験を行い、症状・臨床データの改善を認めた（Terao, Scand J Rheum）。次段階となる臨床治験の論理的根拠を強化するために、本計画において、高安動脈炎患者検体や疾患特異的iPS細胞を用いた基礎実験を行った。今回得られた結果は、p40を標的とする高安動脈炎の新規治療薬開発につながることが示唆された。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis.2018
Author(s)
Terao C, Yoshifuji H, Matsumura T, Naruse TK, Ishii T, Nakaoka Y, Kirino Y, Matsuo K, Origuchi T, Shimizu M, Maejima Y, Amiya E, Tamura N, Kawaguchi T, Takahashi M, Setoh K, Ohmura K, Watanabe R, Horita T, Atsumi T, Matsukura M, Miyata T, et al.
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Journal Title
Proc Natl Acad Sci U S A
Volume: 115
Issue: 51
Pages: 13045-13050
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel susceptibility locus in the IL12B region is associated with the pathophysiology of Takayasu arteritis through IL-12p40 and IL-12p70 production.2017
Author(s)
Nakajima T, Yoshifuji H, Shimizu M, Kitagori K, Murakami K, Nakashima R, Imura Y, Tanaka M, Ohmura K, Matsuda F, Terao C, Mimori T.
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Journal Title
Arthritis Res Ther
Volume: 19
Issue: 1
Pages: 197-197
DOI
Related Report
Peer Reviewed / Open Access
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