The regulatory mechanism of macrophage phagocytosis by secretory hemprotein neudesin

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: NAKAYAMA Yoshiaki 神戸薬科大学, 薬学部, 准教授 (40512455)
• Co-Investigator(Kenkyū-buntansha): 小西 守周 神戸薬科大学, 薬学部, 教授 (00322165) ; 野中 元裕 京都大学, 医学研究科, 准教授 (70514173)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 赤血球代謝 / マクロファージ / サイトカイン / 貪食受容体

Outline of Final Research Achievements

Previous studies primarily focused on the functional analysis of neudesin in the nervous system, and its effects on immune cells remained unknown. We conducted research to investigate the role of the secretory factor neudesin in this regard. Our findings revealed that neudesin regulates the function of red pulp macrophages in the spleen, which recognize and phagocytose aged red blood cells, thereby removing them from circulation. We demonstrated that neudesin controls the metabolism of circulating red blood cells. Specifically, neudesin directly acts on macrophages and suppresses the cell surface expression of Fcγ receptors involved in the phagocytosis of aged red blood cells. This leads to the inhibition of metabolic processes in aged red blood cells. Consequently, neudesin functions as a novel phagocytosis-inhibitory cytokine.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

赤血球は酸素を身体中に運ぶ重要な役割を果たしているが、正常に老化赤血球が体内循環から取り除かれないまま老化赤血球の蓄積が起こると、毛細血管の閉塞や体中への酸素供給不全につながることが知られており、血液の正常な機能に悪影響を及ぼすことがある。本研究により分泌因子neudesinが赤血球の代謝を制御することが明らかにしたことから、neudesinシグナルを制御することにより、赤血球の代謝促進や、貧血あるいは造血障害などの赤血球関連疾患において新たな治療法の開発につながることが期待される。