Study of inflammatory loop mechanism caused by virus-infected cells in HAM pathogenesis.
Project/Area Number |
16K09701
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | St. Marianna University School of Medicine |
Principal Investigator |
Araya Natsumi 聖マリアンナ医科大学, 医学研究科, 助教 (80440353)
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Research Collaborator |
Takahashi Katsunori
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | HTLV-1 / HAM / CXCL10 / CXCR3 / 炎症 |
Outline of Final Research Achievements |
From recent our studies, we suggested that the cross-talk between HTLV-1-infected cells and CXCL10 produced from astrocytes in the spinal cord is important for the formation and maintenance of HTLV-1-related myelopathy (HAM). In this study, to test this hypothesis, I analyzed the HAM model mice which were created by implanting HAM-PBMC into the most highly immunodeficient mice that express CXCL10 specifically in the central nervous system (HAM-PBMC-NSG/GFAP-CXCL10 mice). As results, I proved the infiltration of lymphocytes and infected cells into the central nervous system in HAM-PBMC-NSG/GFAP-CXCL10 mice. In the future, we intend to prove the usefulness as a HAM disease state analysis model by establishing the similarities between the mouse and the HAM disease state by detailed analysis.
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Academic Significance and Societal Importance of the Research Achievements |
HAMは先進国の中でその患者が多いのは日本のみであるため、HAMの病態や発症予防法・治療法に関する我が国での研究成果は世界中から期待されておりその責任は重い。未だHAMには有効な治療法が無く、新規治療薬開発が強く要望されている。HAM 治療法の開発には、ヒトのHAM病態を忠実に再現した動物モデルの必要性が高い。これまでに感染T細胞の細胞浸潤に起因する脊髄障害をきたすHAM病態を再現した動物は得られていない。本研究では、世界初のヒト免疫系を再現したHAMモデルマウスの作製を目指し、HAM病態機序の解明、疾患の診断、予防、治療法の発展に寄与したいと考える。
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Report
(4 results)
Research Products
(32 results)
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[Journal Article] Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity.2018
Author(s)
Sato T, Yagishita N, Tamaki K, Inoue E, Hasegawa D, Nagasaka M, Suzuki H, Araya N, Ariella Coler-Reilly, Hasegawa Y, Tsuboi Y, Takata A, Yamano Y.
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Journal Title
Front Microbiol
Volume: 25(9)
Pages: 1651-1651
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mogamulizumab (Anti-CCR4) in HTLV-1-Associated Myelopathy.2018
Author(s)
Sato T, Coler-Reilly ALG, Yagishita N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y, Yamano Y.
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Journal Title
N Engl J Med.
Volume: 378(6)
Issue: 6
Pages: 529-538
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effectiveness of Daily Prednisolone to Slow Progression of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis: A Multi-Center Retrospective Cohort Study.2017
Author(s)
Coler-Reilly ALG, Sato T, Matsuzaki T, Nakagawa M, Niino M, Nagai M, Nakamura T, Takenouchi N, Araya N, Yagishita N, Inoue E, Yamano Y.
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Journal Title
Neurotherapeutics
Volume: 14(4)
Issue: 4
Pages: 1084-1094
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Daily Prednisolone Slows the Progression of HAM/TSP2017
Author(s)
Ariella L. G. Coler-Reilly, Sato Tomoo, Matsuzaki Toshio, Nakagawa Masanori, Niino Masaaki, Nagai Masahiro, Nakamura Tatsufumi, Takenouchi Norihiro, Araya natsumi, Yagishita Naoko, Yamano Yoshihisa
Organizer
The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
東京都千代田区 〔Grand Arc Hanzomon〕
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Patient Satisfaction Survey for HAM-net Registrants2017
Author(s)
Suzuki Hiroko,Sato Kentaro,Kikuchi Takayuki,Kimura Miyuna,Arifuku Hirotaka,Komita Midori,Shimada Kanade,Seki Kurumi,Tachibana Marika,Yagishita Naoko,Ariella Coler-Reilly,Sato Tomoo,Araya Natsumi,Ishikawa Miho,Koike Mikako,Saito Yumi,Takata Ayako,Yamano Yoshihisa
Organizer
The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
東京都千代田区 〔Grand Arc Hanzomon〕
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Comparative Transcriptome Analysis of HTLV-1-infected Cells and ATL Cells2017
Author(s)
Yamagishi Makoto, Nakano Kazumi, Fujikawa Dai, Kobayashi Seiichiro, Araya Natsumi, Sato Tomoo, Yagishita Naoko, Iwanaga Masako, Utsunomiya Atae, Tanaka Yuetsu , Yamano Yoshihisa, Watanabe Toshiki, Uchimaru Kaoru
Organizer
The 18th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
東京都千代田区 〔Grand Arc Hanzomon〕
Year and Date
2017-03-07
Related Report
Int'l Joint Research
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[Presentation] Phase 1/2a study of Mogamulizumab, an anti-CCR4 monoclonal antibody, in patients with HTLV-1-associated myelopathy (HAM/TSP).2017
Author(s)
Yamano Y, Sato T, A. Coler-Reilly, Yanagisawa N, Araya N, Inoue E, Furuta R, Watanabe T, Uchimaru K, Matsuoka M, Matsumoto N, Hasegawa Y.
Organizer
XXIII World Congress of Neurology
Related Report
Int'l Joint Research
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