Function of tissue macrophages and regulatory T cells after ischemic heart injury

• Project/Area Number: 18K15129
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Keio University
• Principal Investigator: Komai Kyoko 慶應義塾大学, 医学部, 特任助教 (80574590)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2021: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2020: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 組織マクロファージ / CD8陽性T細胞 / 炎症 / 心肥大 / 組織修復 / 心臓組織マクロファージ / 心筋細胞肥大 / 制御性T細胞

Outline of Final Research Achievements

Tissue maintenance is a constant process, and one of the main players in the heart is Ly6clow macrophages (Ly6clow Mac). We aimed to clarify the role of macrophages and T cells in the process of inflammatory convergence and tissue repair in a pressure-loaded cardiac hypertrophy model of transverse aortic constriction (TAC; Transverse aortic constriction). In analysis of cardiac CD45-positive cells in TAC model, we observed a proliferation of Ly6clow Mac. The absence of T cells, especially CD8 positive T cells, leads to greater proliferation of Ly6clowMac, changes the nature of hypertrophic cardiomyocytes, and reduces heart failure in the chronic phase.

Academic Significance and Societal Importance of the Research Achievements

循環器疾患は我が国の死因の第２位であり、慢性の心不全状態となると、その5年生存率は50％とよくない。また、高齢化に従って患者数は今後益々増加することが予想されている。心不全状態の心臓では炎症が起こっているにもかかわらず、未だ有効な免疫療法がない。本研究は炎症の収束と組織修復におけるマクロファージとT細胞の役割を明らかにすることで、有効な免疫療法につなげることを目的とした。これまでにLy6clowMacとCD8陽性T細胞、および心不全の関係を示した研究は少なく、さらなる研究が進むことにより新たな治療法の開発につながると考えられる。

Research Products

• [Journal Article] Single-Cell Analysis Revealed the Role of CD8+ Effector T Cells in Preventing Cardioprotective Macrophage Differentiation in the Early Phase of Heart Failure (2021)
  • Author(s): Komai Kyoko、Ito Minako、Nomura Seitaro、Shichino Shigeyuki、Katoh Manami、Yamada Shintaro、Ko Toshiyuki、Iizuka-Koga Mana、Nakatsukasa Hiroko、Yoshimura Akihiko
  • Journal Title: Frontiers in Immunology Volume: 12 Pages: 763647-763647
  • DOI: 10.3389/fimmu.2021.763647
  • Peer Reviewed / Open Access
• [Journal Article] Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery (2019)
  • Author(s): Ito Minako、Komai Kyoko、Mise-Omata Setsuko、Iizuka-Koga Mana、Noguchi Yoshiko、Kondo Taisuke、Sakai Ryota、Matsuo Kazuhiko、Nakayama Takashi、Yoshie Osamu、Nakatsukasa Hiroko、Chikuma Shunsuke、Shichita Takashi、Yoshimura Akihiko
  • Journal Title: Nature Volume: 565 Issue: 7738 Pages: 246-250
  • DOI: 10.1038/s41586-018-0824-5
  • Peer Reviewed / Open Access