Mechanisms for cell surface expression of chromatin in apoptotic cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03600
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: IWABUCHI Kuniyoshi 金沢医科大学, 医学部, 教授 (10232696)
• Co-Investigator(Kenkyū-buntansha): 逆井 良 金沢医科大学, 医学部, 准教授 (10549950) ; 松井 理 金沢医科大学, 医学部, 助教 (60288272) ; 砂谷 優実 金沢医科大学, 医学部, 講師 (70581057)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: アポトーシス

Outline of Final Research Achievements

Apoptotic cells express a variety of eat-me signals on the surface of cell membrane. Apoptotic cells are quickly removed by macrophages. When this apoptotic cell-removal is inefficient, the histone and DNA on the surface of apoptotic cells are believed to trigger auto-antibody production, which then leads to autoimmune diseases, such as systemic lupus erythematosus. We found that deficiency of DNA repair protein 53BP1 slightly reduced cell surface chromatin, one of the eat-me signals, in apoptotic cells. Furthermore, 53BP1-Tudor domain was required for the chromatin exposure in apoptotic cells.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

生体内で死に陥った細胞はマクロファージにより速やかに貪食され除去される。このメカニズムに障害が起こると、死細胞の表面に露出しているDNAやタンパク質が抗原となり自己抗体が産生されるとされている。本研究の成果は、SLEを代表とする自己免疫疾患の発症メカニズムに大きな知見を与える可能性がある。