New paradigm for the regulation of chronic inflammation by glycosphingolipids

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03452
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Osaka University (2023); Tohoku Medical and Pharmaceutical University (2020-2022)
• Principal Investigator: Inokuchi Jinichi 大阪大学, 大学院理学研究科, 特任教授(常勤) (70131810)
• Co-Investigator(Kenkyū-buntansha): 狩野 裕考 東北医科薬科大学, 薬学部, 助教 (40774279) ; 稲森 啓一郎 東北医科薬科大学, 薬学部, 准教授 (70710375) ; 新田 昂大 東北医科薬科大学, 薬学部, ポスト・ドクター (30847976)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ガングリオシドGM3 / 内因性リガンド / DAMPs(アラーミン) / PAMPs / 肥満 / TLR4 / Caspase4/11 / 炎症性細胞死(パイロトーシス)

Outline of Final Research Achievements

GM3 is the major ganglioside in human blood. We found that very long-chain GM3s (e.g. acyl chain lengths C22, C24) strongly promote the activation of TLR4 by LPS and the representative alarmin HMGB1, whereas long-chain GM3s (e.g. C16, C18) suppress TLR4 activation, indicating that they are "endogenous The results show that long-chain GM3 (C16, C18, etc.) is an "endogenous ligand" that positively and negatively regulates TLR4 activation. Furthermore, very long-chain GM3 greatly enhances Casp4/11-mediated pyrtosis, whereas long-chain GM3 strongly suppresses these responses. The study revealed that "GM3 is a bioactive lipid that regulates these lipopolysaccharide receptors in both positive and negative directions due to its molecular species diversity."

Free Research Field

免疫糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

本課題の推進により、GM3分子種の発現バランスが自然免疫受容体を介して生体恒常性を制御する新機構と、その破綻による疾患発症機序が解明され、GM3の広範な医薬応用性が世界に先駆けて提示されるものと期待される。