Interleukin-27 dependent loss of memory CD4+ T-cells after malaria infection
Project/Area Number |
19K07528
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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 |
Review Section |
Basic Section 49040:Parasitology-related
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Research Institution | Kobe Women's University |
Principal Investigator |
Kimura Daisuke 神戸女子大学, 健康福祉学部, 教授 (50423637)
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Co-Investigator(Kenkyū-buntansha) |
由井 克之 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90274638)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | マラリア / 免疫記憶 / CD4陽性T細胞 / アポトーシス / 溶血性貧血 / T細胞 / IL-27 / CD4+T細胞 |
Outline of Research at the Start |
マラリアに対する有効なワクチンはこれまでに開発されておらず、その原因の1つにマラリアでは免疫記憶が成立しにくいことが挙げられる。我々は、抑制因子IL-27を産生する新規制御性CD4+T細胞「Tr27」を見出し、マラリアにおける免疫抑制機構を報告した。さらに最近、抑制因子IL-27は記憶CD4+T細胞の形成・維持を阻害する結果を得た。本研究計画では、マラリア原虫特異的CD4+T細胞をモニター可能な系を用いて、IL-27による免疫記憶抑制のメカニズムを明らかにする。本研究成果は、マラリアにおける免疫記憶抑制の解除法開発へつながる基礎研究である。
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Outline of Final Research Achievements |
The reason why malaria is difficult to control is that Plasmodium falciparum infection does not maintain immune memory. Previously, we have shown that in a mouse model of malaria infection, activated CD4+ T cells die early after infection, but not in IL-27 receptor-deficient mice. Interestingly, this phenomenon was also observed in mice with drug-induced hemolytic anemia. This suggests that erythrocyte components destroyed by the malaria parasite prevent long-term survival of malaria-specific CD4+ T cells. The relationship between erythrocyte components and IL-27 signaling is currently being analyzed.
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Academic Significance and Societal Importance of the Research Achievements |
本研究目的である「IL-27による免疫記憶抑制メカニズム解明」は、これまでの我々独自の研究成果を発展させたものである。また、記憶T細胞の細胞死を誘発させる赤血球成分を特定できれば、記憶抑制メカニズムが明らかとなり、将来完成が期待されるワクチン効果を促進・維持させることで、マラリアワクチン開発へ向けて貢献ができる。また、これまで研究されてきた既存のワクチン候補中に本研究成果と組み合わせることで、効果が期待できる可能性も考えられる。
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Report
(5 results)
Research Products
(7 results)
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[Journal Article] Type I interferon production elicits differential CD4+ T-cell responses in mice infected with Plasmodium berghei ANKA and P. chabaudi2022
Author(s)
M Ntita, S-I Inoue, J-Yu Jian, G Bayarsaikhan, K Kimura, D Kimura, M Miyakoda E Nozaki, T Sakurai, D Fernandez-Ruiz, WR. Heath, K Yui.
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Journal Title
International Immunology
Volume: 34
Issue: 1
Pages: 21-33
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] CD49d marks Th1 and Tfh-like antigen-specific CD4+ T cells during Plasmodium chabaudi infection2021
Author(s)
Jian JY, Inoue SI, Bayarsaikhan G, Miyakoda M, Kimura D, Kimura K, Nozaki E, Sakurai T, Fernandez-Ruiz D, Heath WR, Yui K.
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Journal Title
International Immunology
Volume: 33
Issue: 8
Pages: 409-422
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] IL-27 inhibits the generation and/or maintenance of Plasmodium-specific memory CD4+ T cells during malaria infection2021
Author(s)
Maria Lourdes Macalinao, Shin-Ichi Inoue, Sanjaadorj Tsogtsaikhan, Ganchimeg Bayarsaikhan, Jiun-Yu Jian, Kazumi Kimura, Daniel Fernandez-Ruiz, William R. Heath, Julius Hafalla, Hiroki Yoshida, Daisuke Kimura, Katsuyuki Yui
Organizer
第90回日本寄生虫学会大会
Related Report
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[Presentation] Transient IL-27 blockade enhances CD4+ T cell memory and protection against malaria2021
Author(s)
Maria Lourdes Macalinao, Shin-Ichi Inoue, Sanjaadorj Tsogtsaikhan, Jiun-Yu Jian, Ganchimeg Bayarsaikhan, Kazumi Kimura, Daniel Fernandez-Ruiz, William R. Heath, Julius Hafalla, Hiroki Yoshida, Daisuke Kimura, Katsuyuki Yui
Organizer
第50回日本免疫学会総会・学術集会
Related Report
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