Proposal of a novel therapeutic concept for cerebral ischemic disease by regulation of efferocytosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03766
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: University of Tsukuba
• Principal Investigator: Nakahashi-Oda Chigusa 筑波大学, 医学医療系, 助教 (50510054)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脳梗塞 / 死細胞貪食 / 免疫受容体 / マクロファージ / CD300a / 炎症

Outline of Final Research Achievements

In this study, we clarified the molecular mechanism of efferocytosis inhibition by the immune system, especially by macrophages and their surface molecule CD300a, in the cerebral infarction cascade of cerebral ischemia, accumulation of dead cells, inflammation, and neuronal damage. In addition, we obtained fundamental findings that will lead to the realization of molecularly targeted therapy for cerebral ischemic diseases by inhibiting CD300a. Specifically, the inhibition of CD300a enhances efferocytosis that emerge as a result of cerebral ischemia and reduces neurological damage after cerebral infarction, suggesting that CD300a is a candidate for molecularly targeted therapy after cerebral infarction.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

脳梗塞においては、神経細胞等の脳細胞が死滅し、死細胞由来の炎症が様々な神経症状を誘導するため、死細胞を早期に除去することができれば、脳梗塞による神経障害を最小限に食い止めることができると考えられる。本研究では、CD300aを欠損、もしくは抗CD300a抗体の投与によってその機能を阻害すると、マクロファージによる死細胞の貪食を亢進させることが可能となり、マウス脳梗塞モデルにおける神経障害が軽減することを見いだした。本研究の成果は、脳梗塞後の神経障害克服の実現へ向けた一歩になるものと期待される。