Analysis of newly identified pathogenic CD4+ helper T-cells in patients with HTLV-1-associated myelopathy
Project/Area Number |
25461294
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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 |
Yamano Yoshihisa 聖マリアンナ医科大学, 医学(系)研究科(研究院), 准教授 (80445882)
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Co-Investigator(Kenkyū-buntansha) |
MISU Tatsuro 東北大学, 医学(系)研究科(研究院), 助教 (00396491)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 内科系臨床医学 / 神経内科学 / 神経病態免疫学 |
Outline of Final Research Achievements |
The main feature of Human T-lymphotropic virus type I (HTLV-1) -associated myelopathy (HAM) pathogenesis is a virus-induced hyperactive immune response that produces chronic inflammation in the central nervous system (CNS), but the mechanism by which HTLV-1 deregulates the immune response is unknown. We recently reported a high frequency of HTLV-1-infected CCR4+ cells, including regulatory T cells. We showed that HTLV-1 induces a Th1-like state in these CCR4+ cells via T-bet expression. We have also found that CXCL10 plays an important role in a positive feedback loop that maintains inflammation in the CNS. Astrocytes, which were found to be the main producers of CXCL10 in the CNS, are another key player in the loop. In short, we postulate that infected CCR4+ Th1-like T cells produce interferon-γ, which stimulates astrocytes to produce CXCL10. We now have a much better understanding of the molecular mechanisms at play in HAM pathogenesis.
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Report
(4 results)
Research Products
(69 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
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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] 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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[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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[Presentation] HAMの治療展望.2015
Author(s)
山野嘉久.
Organizer
第27回日本神経免疫学会学術集会
Place of Presentation
岐阜県岐阜市(長良川国際会議場)
Year and Date
2015-09-15
Related Report
Invited
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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] 難病研究資源バンクにおける収集試料のHLAタイピング実施による難病研究の推進.2014
Author(s)
夛田まや子, 平田誠, 佐々木光穂, 樋野村亜希子, 前畑みどり, 高橋一朗, 増井徹, 山野嘉久, 吉良潤一, 米田悦啓, 坂手龍一.
Organizer
第23回日本組織適合性学会大会
Place of Presentation
長崎県(長崎市)〔長崎大学坂本キャンパス〕
Year and Date
2014-09-13 – 2014-09-15
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] 患者QOLの改善に向けた患者レジストリの満足度調査.2014
Author(s)
菊池崇之, 有福厚孝, 木村未祐奈, 佐藤健太郎, 本橋隆子, 木村美也子, 網中雅仁, 高田礼子, 八木下尚子, 山野嘉久.
Organizer
第55回日本神経学会学術大会
Place of Presentation
福岡県(福岡市)〔福岡国際会議場〕
Year and Date
2014-05-21 – 2014-05-24
Related Report
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[Presentation] CXCL10 and Neopterin in cerebrospinal fluid are Candidate Prognostic Biomarkers for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis.2013
Author(s)
Yamano Y., Sato T., Ando H., Araya N., Yagishita N., Yamauchi J., Coler-Reilly A., Utsunomiya A., Jacobson S., Izumo S.
Organizer
The 16th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Montreal, Canada
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/TSP.2013
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
The 16th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Montreal, Canada
Related Report
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[Presentation] CXCL10, CXCL9 and Neopterin in cerebrospinal fluid as Candidate Prognostic Biomarkers for HAM/TSP.2013
Author(s)
Yamano Y., Sato T., Coler-Reilly A., Ando H., Araya N., Yagishita N., Yamauchi J., Utsunomiya A., Jacobson S., Izumo S.
Organizer
The 16th International Conference on Human Retrovirology: HTLV and Related Viruses
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 system.2013
Author(s)
Coler-Reilly A., Hashimoto M., Yagishita N., Sato T., Ando H., Yamauchi J., Araya N., Kimura M., Yamano Y., Takata A.
Organizer
The 16th International Conference on Human Retrovirology: HTLV and Related Viruses
Place of Presentation
Montreal, Canada
Related Report
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[Presentation] 同種造血幹細胞移植後ATL患者からの新規HTLV-1特異的CD4エピトープの同定(Identification of novel HTLV-1-specific CD4 epitopes in ATL patients after hematopoietic stem cell transplantation.)2013
Author(s)
Hasegawa A., Tamai Y., Takamori A., Sasada A., Tanosaki R., Choi I., Utsunomiya A., Suehiro Y., Maeda Y., Yamano Y., Uike N., Kannagi M.
Organizer
第72回日本癌学会学術総会
Place of Presentation
神奈川県(横浜市)〔パシフィコ横浜〕
Related Report
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