Development of abnormal immune system by regulatory T-cell specific HTLV-1 expression in HAM/TSP
Project/Area Number |
24790898
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
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(系)研究科(研究院), 助教 (80440353)
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Project Period (FY) |
2012-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | HTLV-1 / HTLV-1関連脊髄症 / Tax / 制御性T細胞 / IFN-γ / HTLV-1関連脊髄症(HAM) / HTLV-1関連脊髄症(HAM) |
Outline of Final Research Achievements |
Human T-lymphotropic virus type 1 (HTLV-1) harness CD4+ T-cell plasticity to effect changes in infected T-cells via HTLV-1 Tax that cause once suppressive Treg cells to lose FOXP3 expression and produce IFN-γ. We hypothesized that the transformation of Tax expressed Treg cells plays a key role in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In this study, I created the knock-in mice expressing Tax in treg cells and indicated some abnormal immune responses in this mouse (chronic inflammation of the ear and tail, inflammatory cytokine production from spleen cells and hyper-responsiveness to EAE). Therefore, these results suggested that abnormal immune responses induced by expression of Tax in Treg cells play an important role in development and pathogenesis of HAM/TSP.
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Report
(5 results)
Research Products
(60 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 K, 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
Issue: 8
Pages: 1042-55
DOI
Related Report
Peer Reviewed / Open Access
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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
Issue: 2
Pages: 238-48
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] HTLV-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
Issue: 8
Pages: 3431-42
DOI
Related Report
Peer Reviewed / Open Access
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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(10)
Issue: 10
Pages: e2479-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(Pt9)
Issue: 9
Pages: 2876-2887
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
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
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
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
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
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
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
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
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] 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] 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
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
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
Related Report
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