Innovative approach to anti-MDA5 antibody-positive dermatomyositis; Development of animal models and understanding of pathogenesis
Project/Area Number |
18K19532
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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Research Institution | The University of Tokyo |
Principal Investigator |
Sato Shinichi 東京大学, 医学部附属病院, 教授 (20215792)
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Co-Investigator(Kenkyū-buntansha) |
吉崎 歩 東京大学, 医学部附属病院, 講師 (40530415)
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Project Period (FY) |
2018-06-29 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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Keywords | 皮膚筋炎 / モデル動物 / MD5 / 自己免疫疾患 / MDA5 / 自己抗体 |
Outline of Final Research Achievements |
In this study, we use complete Freund's adjuvant in MDA5-deficient mice to elicit an immune response to the full-length MDA5 peptide and adoptive transfer of immune-responsive cells such as B cells into wild-type mice to generate a mouse model of anti-MDA5 antibody-positive dermatomyositis and analyze the pathogenesis histopathologically, serologically, and cell biologically. Because MDA5 is a self-antigen, tolerance is predicted to be induced and may not be able to elicit an immune response to MDA5. Therefore, we examined whether splenocytes obtained from MDA5-deficient mice immunized with MDA5 can be transfected into wild-type mice by dividing them into T and B cell fractions and inducing pathogenesis. This experiment will also allow the identification of cells that are important for disease development.
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Academic Significance and Societal Importance of the Research Achievements |
これまで抗MDA5抗体陽性皮膚筋炎の研究は十分に行われていない。オーファン疾患である皮膚筋炎において、その亜型と捉えられる本疾患は患者数がごく少数に限られており、検討に足るまとまった症例数が得られないからである。また、抗MDA5抗体が病勢と相関することが知られているにも関わらず、抗MDA5抗体の病原性についても不明な点が多い。MDA5は細胞質内蛋白であり、通常抗体は細胞内には侵入しないため、抗MDA5抗体がどの蛋白をターゲットとして病原性を発揮しているかは、ブラックボックスである。本研究で挑戦したモデル動物の開発は、本疾患の解析に役立ち、病因と病態の解明への道を拓く点で意義深い。
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] A potential contribution of trappin-2 to the development of vasculopathy in systemic sclerosis.2019
Author(s)
Miyagawa T, Asano Y, Saigusa R, Hirabayashi M, Yamashita T, Taniguchi T, Takahashi T, Nakamura K, Miura S, Yoshizaki A, Miyagaki T, Sato S.
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Journal Title
J Eur Acad Dermatol Venereol.
Volume: In press
Issue: 4
Pages: 753-760
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Increased expression of aquaporin-1 in dermal fibroblasts and dermal microvascular endothelial cells possibly contributes to skin fibrosis and edema in patients with systemic sclerosis.2019
Author(s)
Yamashita T, Asano Y, Saigusa R, Taniguchi T, Nakamura K, Miura S, Toyama T, Takahashi T, Ichimura Y, Hirabayashi M, Yoshizaki A, Miyagaki T, Sugaya M, Sato S.
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Journal Title
J Dermatol Sci
Volume: 93
Issue: 1
Pages: 24-32
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Rapid alteration of serum interleukin-6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis-associated interstitial lung disease.2018
Author(s)
Numajiri H, Yoshizaki A, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Sumida H, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S.
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Journal Title
J Dermatol.
Volume: 45
Issue: 10
Pages: 1221-1224
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Rapid alteration of serum interleukin-6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis-associated interstitial lung disease.2018
Author(s)
Numajiri H, Yoshizaki A, Fukasawa T, Ebata S, Nakamura K, Yamashita T, Saigusa R, Miura S, Hirabayashi M, Yoshizaki A, Sumida H, Asano Y, Kazoe Y, Mawatari K, Kitamori T, Sato S.
Organizer
The 5th Eastern Asia Dermatology Congress (EADC2018)
Related Report
Int'l Joint Research / Invited