Elucidation of the antibody production mechanism for next-generation vaccine development
| Project/Area Number |
24590098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
HARADA Yohsuke 東京理科大学, 付置研究所, 助教 (20328579)
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| Co-Investigator(Kenkyū-buntansha) |
KUBO Masato 東京理科大学, 生命医科学研究所, 教授 (40277281)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | T細胞 / B細胞 / ワクチン / 抗体 / 免疫記憶 / Notch / メモリー / Tfh / ヘルパーT細胞 / サイトカイン / 抗体産生 |
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| Outline of Final Research Achievements |
It has been suggested that memory T follicular helper (Tfh) cells are generated and contribute to a secondary humoral response. Thus, to clarify the mechanisms for generation of memory Tfh cells is relevant for effective vaccine design. Here we demonstrate that Notch signaling regulates generation of memory Tfh cells. During contraction phase, up-regulation of CCR7 and down-regulation of CXCR5 brings Tfh cells into the T-B border area, where they are maintained as memory cells. Lack of Notch signaling during initial antigen priming, but not at the contraction phase, led to a failure of memory T cell generation due to abnormal migration caused by defective CCR7 up-regulation. Notch signaling regulated CCR7 expression through suppression of Blimp-1 expression. Our findings indicate that Notch signaling is critical for the generation and function of memory Tfh cells and could be a future target for the vaccination strategy.
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Report
(4 results)
Research Products
(12 results)
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[Presentation] Role of Notch signaling in the generation and function of T follicular helper (TFH) and memory T cells2013
Author(s)
Harada,Y., Tokoyoda, K., Miyauchi, K., Harada,Y., Hanazawa, A., Takemori, T., Kubo, M.
Organizer
The Joint international Meeting of The 78th Meeting of the Japanese Society of Interferon and Cytokine Research and The 21st International Symposium on Molecular Cell Biology of Macrophages
Place of Presentation
Tokyo
Related Report
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[Presentation] Role of Notch signal in function and generation of T follicular helper (TFH) and memory T cells2013
Author(s)
Harada,Y., Tokoyoda, K., Miyauchi, K., Harada,Y., Hanazawa, A., Takemori, T., Kubo, M.
Organizer
The 6th International Workshop of Kyoto T cell Conference
Place of Presentation
Kyoto
Related Report
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[Presentation] Role of Notch signal in the generation of follicular helper T cells (TFH) and memory T cells2013
Author(s)
Harada,Y., Tokoyoda, K., Miyauchi, K., Harada,Y., Hanazawa, A., Ohno, S., Yanagi, Y., Takemori, T., Kubo, M.
Organizer
15th International Congress of Immunology
Place of Presentation
Milan
Related Report
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[Presentation] Role of Notch signaling in the generation and function of T follicular helper (TFH) and memory T cells2013
Author(s)
Harada,Y., Tokoyoda, K., Miyauchi, K., Harada,Y., Hanazawa, A., Takemori, T., Kubo, M.
Organizer
日本免疫学会
Place of Presentation
千葉
Related Report
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