The roll of Kv1.3 and KCa3.1 for the differentiation of effector T cells in patients with heart failure

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Sato Kayoko 東京女子医科大学, 医学部, 講師 (20246482)
• Co-Investigator(Kenkyū-buntansha): 鈴木 敦 東京女子医科大学, 医学部, 助教 (00625626)
• Research Collaborator: HAGIWARA nobuhisa ; NISHII akiko ; KITAMURA kazutaka ; SHIGA tsuyoshi
• Project Period (FY): 2015-04-01 – 2019-03-31
• 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

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.

Free Research Field

循環器内科学。動脈硬化進展および急性冠症候群・更年期女性・心不全における炎症・免疫学的機序の研究。

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。