Elucidation of the regulatory mechanisms of inflammation and immune responses by damage-associated molecules

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H00504
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Taniguchi Tadatsugu 東京大学, 先端科学技術研究センター, 名誉教授 (50133616)
• Co-Investigator(Kenkyū-buntansha): 半谷 匠 東京大学, 先端科学技術研究センター, 客員研究員 (50785350) ; 柳井 秀元 東京大学, 先端科学技術研究センター, 特任准教授 (70431765)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 免疫シグナル伝達 / 炎症 / 自然免疫受容体 / HMGB1 / TCTP / U11snRNA / 腫瘍免疫 / 免疫原性核酸

Outline of Final Research Achievements

In this study, we studied the mechanisms of regulation of inflammatory and immune responses by self-derived molecules called DAMPs (damage-associated molecular patterns). DAMPs are released from damaged or dead cells, thereby contributing to development and/or exacerbating of diseases such as cancer. We analyzed the function of HMGB1 and adduced evidence that the lack of HMGB1 results in exacerbation of sepsis in mice. We newly identified TCTP and spermidine as self-derived molecules that impinge on anti-tumor immune responses and elucidated their mechanisms of action. We also developed the neutralizing antibody for TCTP, and found that the antibody treatment enhances anti-tumor immune responses and suppresses tumor growth.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究において、TCTPやスペルミジンなど、免疫応答の制御に関与する死細胞由来分子を同定した。また細胞外TCTPの作用を阻害することで腫瘍免疫の活性化を増強させ、病態を抑制することが可能であることも示された。HMGB1やU11 snRNAなどについてもさらに検討を加えていくことで、死細胞由来分子による免疫制御機構の全体像の解明につなげていきたい。また、本研究をさらに発展させていくことで、新たな病態抑制法の開発が進むことも期待される。