| Project/Area Number |
15K09129
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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 |
Cardiovascular medicine
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Sato Kayoko 東京女子医科大学, 医学部, 講師 (20246482)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 敦 東京女子医科大学, 医学部, 助教 (00625626)
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| Research Collaborator |
HAGIWARA nobuhisa
NISHII akiko
KITAMURA kazutaka
SHIGA tsuyoshi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 臨床血管学 / 心不全 / Ｔ細胞 / 免疫記憶 / カリウムチャンネル / サイトカイン / 炎症 / 免疫 / T細胞 |
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| Outline of Final Research Achievements |
Japan becomes the super aging society, and heart failure management becomes the important problem for a prognosis of the cardiovascular disease. In this study, we examined contribution of potassium channels KV1.3 and KCa3.1 which controlled a T cell memory in the heart failure exacerbation.
Expression and a function of KV1.3 which promoted effector memory T cells (TEM) differentiation were enhanced more than that of KCa3.1 which promoted central memory T cells (TCM) differentiation in the patients with severe heart failure. Therefore, the ratios of cytotoxic effector T cells (Teff) Th1 and CD8 CTL T cells increased and increase of inflammatory cytokine IFN γ and Granzyme B was induced, and, as a result, the exacerbation of heart failure might be occurred.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、はじめて心不全の病態増悪に関与するT細胞メモリー機構が明らかとなった。重症心不全では細胞障害性の強いTeffが多く、分化初期段階であるTEM分化に重要なKV1.3の発現と機能亢進が認められた。
カリウムチャンネルは多様なサブファミリーを形成するが、KV1.3は免疫細胞に特異的に機能発現しており、KV1.3阻害剤の開発はTEM抑制効果を有するため、安全性の高い創薬標的と期待される。
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