Modulation of immune memory in blood stem cell toward effective host defense

2023 Fiscal Year Final Research Report

• Project/Area Number: 21KK0150
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Kumamoto University
• Principal Investigator: Takizawa Hitoshi 熊本大学, 国際先端医学研究機構, 特別招聘教授 (10630866)
• Co-Investigator(Kenkyū-buntansha): HO Pui・Yu 熊本大学, 国際先端医学研究機構, 特定事業研究員 (40888385) ; 山下 真幸 東京大学, 医科学研究所, 助教 (80588038) ; 河合 麻友 (徳舛麻友) 熊本大学, 国際先端医学研究機構, 特定事業研究員 (50942687)
• Project Period (FY): 2021-10-07 – 2024-03-31
• Keywords: 造血幹細胞

Outline of Final Research Achievements

Hematopoietic stem cells are cells that serve as a source for producing blood and immune systems throughout life. They have the ability to self-replicate within the bone marrow and differentiate into various cells. In this research project, we have tested the hypothesis of "immunomodulation (priming) of stem cell immunity," which involves inducing immune memory in aged hematopoietic stem cells through natural immune signals to construct a more responsive blood and immune system against infections and inflammation. The results obtained in this study strongly suggest that epigenetic changes resembling memory occur in hematopoietic stem cells and alters their responsiveness to secondary stimuli such as infection and inflammation. The future focus will be on identifying responsible genes for natural immune memory and establishing methodologies to enhance blood and immune function through their control.

Free Research Field

血液学

Academic Significance and Societal Importance of the Research Achievements

自然免疫応答は、本来は生体防御のために免疫細胞に賦与されたもので、造血幹細胞などの未熟な造血細胞でもTLR機能が見つかり感染時の造血産生に重要である。本研究では、Bacteroides属の菌体成分が腸炎後の組織修復に寄与する好中球を誘導するユニークな性質を見出した（特許取得済み）。本菌体成分はグラム陰性菌由来分子のリポ多糖 (LPS)と比べて、造血幹細胞の機能を障害することも強い炎症を起こすこともなく、造血幹細胞にエピゲノム変化を誘導できる優位性を有することが示された。今後は、プライミングを誘導する分子やシグナルを同定し次第、ワクチン開発や薬剤製品化につなげていきたい。