Pathogenicity of Treg-derived Th1-like cells identified in patients with HTLV-1-associated myelopathy
Project/Area Number |
25461293
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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 |
Sato Tomoo 聖マリアンナ医科大学, 医学(系)研究科(研究院), 講師 (30387063)
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Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | HTLV-1 / Tax / 制御性T細胞 / HTLV-1関連脊髄症 |
Outline of Final Research Achievements |
Recently, we reported that HTLV-1 induces Treg-derived Th1-like cells via the viral protein Tax in patients with HTLV-1-associated myelopathy. However, the pathogenicity of the Treg-derived Th1-like cells induced by Tax remains unclear. In order to investigate the pathogenicity of the cells, we established mice that expressed Tax specifically in Treg (Foxp3+ cells). All the mice that expressed Tax in all of the Foxp3+ cells died in 6 weeks, and almost all the mice that expressed Tax in some of the Foxp3+ cells showed chronic ear skin inflammation and chronic tail skin ulcer. These results suggest that HTLV-1 tax may modulate Treg function of the Foxp3+ cells and Tax-expressing Foxp3+ cells induce chronic inflammatory conditions in mice.
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Report
(4 results)
Research Products
(54 results)
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[Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β.2015
Author(s)
Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara KI, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
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Journal Title
EMBO J
Volume: 34(8)
Pages: 1042-1055
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Mogamulizumab, an anti-CCR4 antibody, targets human T-lymphotropic virus type 1-infected CD8+ and CD4+ T cells to treat associated myelopathy.2015
Author(s)
Yamauchi J, Coler-Reilly A, Sato T, Araya N, Yagishita N, Ando H, Kunitomo Y, Takahashi K, Tanaka Y, Shibagaki Y, Nishioka K, Nakajima T, Hasegawa Y, Utsunomiya A, Kimura K, Yamano Y.
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Journal Title
J Infect Dis
Volume: 211(2)
Pages: 238-248
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] HLVL-1 induces a Th1-like state in CD4+CCR4+ T cells.2014
Author(s)
Araya N, Sato T, Ando H, Tomaru U, Yoshida M, Coler-Reilly A, Yagishita N, Yamauchi J, Hasegawa A, Kannagi M, Hasegawa Y, Takahashi K, Kunitomo Y, Tanaka Y, Nakajima T, Nishioka K, Utsunomiya A, Jacobson S, Yamano Y.
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Journal Title
J Clin Invest
Volume: 124(8)
Pages: 3431-3442
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Serum level of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of disease activity in relapsing polychondritis.2014
Author(s)
Sato T, Yamano Y, Tomaru U, Shimizu Y, Ando H, Okazaki T, Nagafuchi H, Shimizu J, Ozaki S, Miyazawa T, Yudoh K, Oka H, Suzuki N.
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Journal Title
Modern Rheumatology
Volume: 24
Pages: 129-136
DOI
Related Report
Peer Reviewed
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[Journal Article] CSF CXCL10, CXCL9, and Neopterin as Candidate Prognostic Biomarkers for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.2013
Author(s)
Sato T, Coler-Reilly A, Utsunomiya A, Araya N, Yagishita N, Ando H, Yamauchi J, Inoue E, Ueno T, Hasegawa Y, Nishioka K, Nakajima T, Jacobson S, Izumo S, Yamano Y.
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Journal Title
PLoS Negl Trop Dis
Volume: 7
Pages: e2479
DOI
Related Report
Peer Reviewed
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[Journal Article] Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy.2013
Author(s)
Ando H, Sato T, Tomaru U, Yoshida M, Utsunomiya A, Yamauchi J, Araya N, Yagishita N, Coler-Reilly A, Shimizu Y, Yudoh K, Hasegawa Y, Nishioka K, Nakajima T, Jacobson S, Yamano Y.
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Journal Title
Brain
Volume: 136
Pages: 2876-87
DOI
Related Report
Peer Reviewed
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[Presentation] Humanized anti-CCR4 antibody KW0761 targets HTLV-1-infected CD4+CCR4+ and CD8+CCR4+ T-cells to treat HAM/TSP.2015
Author(s)
Yamano Y, Yamauchi J, Coler-Reilly A, Sato T, Araya N, Yagishita N, Kunitomo Y, Takahashi K, Tanaka Y, Akiyama H, Hasegawa Y, Utsunomiya A.
Organizer
17th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Martinique, Frenchi West Indies
Year and Date
2015-06-18 – 2015-06-21
Related Report
Int'l Joint Research
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[Presentation] HTLV-1 Tax induces Th1 master regulator T-bet and thus IFN-γ in CD4+CCR4+ T-cells of virus-associated myelopathy patients.2015
Author(s)
Araya N, Sato T, Tomaru U, Coler-Reilly A, Yagishita N, Yamauchi J, Hasegawa A, Kannagi M, Akiyama H,Hasegawa Y, Takahashi K, Kunitomo Y, Tanaka Y, Utsunomiya A, Jacobson S, Yamano Y.
Organizer
17th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Martinique, Frenchi West Indies
Year and Date
2015-06-18 – 2015-06-21
Related Report
Int'l Joint Research
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[Presentation] HAM-net national patient registration system reveals details of how Japanese patients with HTLV-1-associated myelopathy/tropical spastic paraparesis progress over time.2015
Author(s)
Coler-Reilly A, Yagishita N, Sato T, Araya N, Ishikawa M, Koike M, Saito Y, Suzuki H, Yamano Y, Takata A.
Organizer
17th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Martinique, Frenchi West Indies
Year and Date
2015-06-18 – 2015-06-21
Related Report
Int'l Joint Research
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[Presentation] Characteristics of HAM/TSP after kidney transplantation from HTLV-1 positive living donors.2015
Author(s)
Kimura M, Yamauchi J, Taisho H, Sato T, Yagishita N, Araya N, Sato K, Kikuchi T, Hasegawa Y, Chikaraishi T, Shibagaki Y, Yamano Y.
Organizer
17th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Martinique, Frenchi West Indies
Year and Date
2015-06-18 – 2015-06-21
Related Report
Int'l Joint Research
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[Presentation] Patient Satisfaction Survey for HAM-net Registrants.2015
Author(s)
Sato K, Kikuchi T, Kimura M, Komita M,Shimada K, Seki K, Tachibana M, Yagishita N, Coler-Reilly A, Sato T, Arayta N, Ishikawa M, Koike M, Saito Y, Suzuki H, Takata A, Yamano Y.
Organizer
17th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Martinique, Frenchi West Indies
Year and Date
2015-06-18 – 2015-06-21
Related Report
Int'l Joint Research
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[Presentation] Evaluation of clinical outcome measures for HAM/TSP.2015
Author(s)
Kikuchi T, Sawabe A, Negishi Y, Noda A, Hirai Y, Inoue E, Kimura M, Sato K, Araya N, Yagishita N, Sato T, Yamano Y.
Organizer
17th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Martinique, Frenchi West Indies
Year and Date
2015-06-18 – 2015-06-21
Related Report
Int'l Joint Research
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[Presentation] 患者レジストリへの介入方法と患者満足度の変化.2015
Author(s)
佐藤健太郎, 菊池崇之, 木村未祐奈, 込田みどり, 島田奏, 関来未, 橘茉莉花, 八木下尚子, 佐藤知雄, 新谷奈津美, 石川美穂, 小池美佳子, 齋藤祐美, 鈴木弘子, 高田礼子, 山野嘉久.
Organizer
第56回日本神経学会学術大会
Place of Presentation
朱鷺メッセ(新潟県新潟市)
Year and Date
2015-05-20 – 2015-05-23
Related Report
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[Presentation] HAM患者レジストリ「HAMねっと」を活用した経年的前向き調査.2015
Author(s)
木村未祐奈, 佐藤健太郎, 菊池崇之, 八木下尚子, 新谷奈津美, 石川美穂, 小池美佳子, 齋藤祐美, 佐藤知雄, 鈴木弘子, 木村美也子, 高田礼子, 山野嘉久.
Organizer
第56回日本神経学会学術大会
Place of Presentation
朱鷺メッセ(新潟県新潟市)
Year and Date
2015-05-20 – 2015-05-23
Related Report
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[Presentation] 希少難病HAMの臨床的有効性評価指標の検討.2015
Author(s)
沢辺愛加, 根岸由衣, 野田和里, 平井祐士, 井上永介, 新谷奈津美, 八木下尚子, 佐藤知雄, 山野嘉久.
Organizer
第56回日本神経学会学術大会
Place of Presentation
朱鷺メッセ(新潟県新潟市)
Year and Date
2015-05-20 – 2015-05-23
Related Report
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[Presentation] HAM患者登録システム「HAMねっと」を用いた疫学的解析.2014
Author(s)
山野嘉久, 木村美也子, 八木下尚子, 鈴木弘子, 石川美穂, 小池美佳子, 齊藤 祐美, 新谷奈津美, 佐藤知雄, 高田礼子.
Organizer
第1回日本HTLV-1学会学術集会
Place of Presentation
東京都(港区)〔東京大学医科学研究所〕
Year and Date
2014-08-22 – 2014-08-24
Related Report
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[Presentation] HTLV-1によるHTLV-1関連脊髄症(HAM)病原性T細胞の発生機構の解析.2014
Author(s)
新谷奈津美, 佐藤知雄, 安藤仁, 外丸詩野, Ariella Coler-Reilly, 八木下尚子, 山内淳司, 長谷川温彦, 神奈木真理, 田中勇悦, 宇都宮與, 山野嘉久.
Organizer
第1回日本HTLV-1学会学術集会
Place of Presentation
東京都(港区)〔東京大学医科学研究所〕
Year and Date
2014-08-22 – 2014-08-24
Related Report
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[Presentation] HTLV-1関連脊髄症(HAM)患者登録システム「HAMねっと」の患者満足度調査.2014
Author(s)
八木下尚子, 有福厚孝, 菊池崇之, 木村未祐奈, 佐藤健太郎, 石川美穂, 鈴木弘子, 小池美佳子, 齊藤祐美, 新谷奈津美, 佐藤知雄, 木村美也子, 高田礼子, 山野嘉久.
Organizer
第1回日本HTLV-1学会学術集会
Place of Presentation
東京都(港区)〔東京大学医科学研究所〕
Year and Date
2014-08-22 – 2014-08-24
Related Report
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[Presentation] HAMにおける抗CCR4抗体製剤の有用性に関する検討2013
Author(s)
山野嘉久, 山内淳司, 新谷奈津美, 安藤仁, Ariella Color-Reilly, 八木下尚子, 宇都宮與, 佐藤知雄.
Organizer
第25回日本神経免疫学会学術集会
Place of Presentation
山口県(下関市)〔海峡メッセ下関〕
Year and Date
20131127-20131129
Related Report
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[Presentation] Virus-induced CXCL10-CXCR3 positive feedback loop via astrocytes is critical for maintaining chronic inflammatory lesions in HAM/TSP2013
Author(s)
Sato T, Ando H, Tomaru U, Yoshida M, Utsunomiya A, Yamauchi J, Araya N, Yagishita N, Coler-Reilly A, Jacobson S, Yamano Y
Organizer
16th International conference on human retrovirology: HTLV and related retroviruses
Place of Presentation
Montreal, Canada
Year and Date
20130626-20130630
Related Report
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[Presentation] CXCL10 and neopterin in CSF are candidate prognostic biomarkers for HTLV-1-associated myelopathy/tropical spastic paraparesis2013
Author(s)
Yamano Y, Sato T, Ando H, Araya N, Yagishita N, Yamauchi J, Coler-Reilly A, Utsunomiya A, Jacobson S, Izumo S
Organizer
16th International conference on human retrovirology: HTLV and related retroviruses
Place of Presentation
Montreal, Canada
Year and Date
20130626-20130630
Related Report
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[Presentation] Nation-wide epidemiological study in Japan on HTLV-1 associated myelopathy/tropical spastic paraparesis using HAM-net, a novel patient registration system2013
Author(s)
Coler-Reilly A, Hashimoto M, Yagishita N, Sato T, Ando H, Yamauchi J, Araya N, Kimura M, Yamano Y, Takata A
Organizer
16th International conference on human retrovirology: HTLV and related retroviruses
Place of Presentation
Montreal, Canada
Year and Date
20130626-20130630
Related Report
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[Presentation] Label free quantitative proteome analysis on cerebrospinal fluid to discover severity grade markers for Human T-cell leukemia virus type 1 associated myelopathy/tropic spastic paraparesis (HAM/TSP)
Author(s)
Makoto Ishihara, Natsumi Araya, Tomoo Sato, Risa Fujii, Ayako Tatsuguchi, Naomi Saichi, Hidewaki Nakagawa, Yoshihisa Yamano, Koji Ueda
Organizer
HUPO 2013
Place of Presentation
Pacifico Yocohama, Kanagawa, Japan
Related Report
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