Molecular mechanisms of immunological memory control by a nuclear receptor REV-ERB and its application to vaccines

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02375
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42030:Animal life science-related
• Research Institution: Hokkaido University
• Principal Investigator: Takada Kensuke 北海道大学, ワクチン研究開発拠点, 特任准教授 (40570073)
• Co-Investigator(Kenkyū-buntansha): 稲葉 睦 北海道大学, 獣医学研究院, 教授 (00183179)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 免疫 / 生体防御 / 免疫記憶 / T細胞

Outline of Final Research Achievements

A part of activated lymphocytes differentiate into memory lymphocytes and contribute to the body protection against the reinfection with specific pathogen. Elucidating the mechanisms that control memory T cell differentiation is essential for the development of immunotherapy mediated by cellular immune memory. In this study, we focused on a nuclear receptor REV-ERB, which is highly expressed in memory T cells, and investigated its relevance to the immune response and memory formation of CD8+ T cells . We revealed that activation of REV-ERB promotes the differentiation of a specific memory T cell subpopulation, and found several candidate molecules that might be responsible for this lineage bias in post-activated T cells. Furthermore, we have established the technical basis to directly examine the involvement of REV-ERB in T cell immune responses to infection using REV-ERB-deficient T cells.

Free Research Field

免疫学、動物生命科学

Academic Significance and Societal Importance of the Research Achievements

免疫系は一度感染した病原体を記憶し、再感染に対して素早く強力に応答する（免疫記憶）。免疫記憶の本体は、抗原特異的に活性化した後、抗原排除後も長期にわたって体内で維持される記憶リンパ球であるが、その分化や維持を担う制御機構には未解明の部分が多い。本研究は、細胞内病原体や癌細胞の排除に中心的な役割を果たすCD8+ T細胞の記憶形成を制御する分子を探索し、転写制御因子としての機能をもつ核内受容体が関与する可能性を見出した。今後の研究の発展によって、学術的貢献と臨床応用が期待される。