Regulation in affinity of Fc receptor by sphingolipids

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08283
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Keio University
• Principal Investigator: OKUBO Koshu 慶應義塾大学, 医学部(信濃町), 共同研究員 (60749125)
• Co-Investigator(Kenkyū-buntansha): 平橋 淳一 慶應義塾大学, 医学部(信濃町), 講師 (70296573)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Fc受容体

Outline of Final Research Achievements

Lactosylceramide, one of shingolipids, and its ligand β-glucan activates intracellular phosphorylation pathway including Lyn kinase and SHP-1. Downstream target of this pathway was ITAM of FcγRIIA, and could relate to ROS generation system such as NADPH oxidase or PKCδ. Attachment of immune complex and FcγRIIA was dependent on STIM1 or PKCδ. And neutrophil's effector function of FcγRIIA was regulated by STIM1 or PKCδ.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではβ-glucan/LacCer/Lyn/SHP-1という一連の経路について、そのメカニズムとしてFcγ受容体IIAのITAMのリン酸化の関与や重要な分子STIM1やPKCδの関わりを示した。その意義はこの経路が発症に関わるとされている疾患群、例えばループス腎炎などの自己免疫性腎炎に対する、腎臓機能の保護、生命予後の改善のための創薬対象の探索に役立つという意義がある。