Analysis of function of mTORC2 as fatty acid sensor in TLR3 response

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16685
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Sato Ryota 東京大学, 医科学研究所, 助教 (90779703)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: TLR / 自然免疫 / ウイルス学 / 代謝免疫学

Outline of Final Research Achievements

mTOR forms two complexes, mTORC1 and mTORC2. Our previous research revealed mTORC2 is master regulatory molecule in TLR3 response, but a role as a metabolic sensor of mTORC2 was still unclear.
We obtained fatty acid synthesis pathway-related molecules as candidates by gRNA library screening. TLR3 responses were attenuated in these knockout cells compared with wild type. It was confirmed that the removal of fatty acids reduced the intracellular translocation of TLR3 stimulated by the TLR3 ligand poly (I: C), and that the addition of fatty acids restored it. This indicates that mTORC2 may sense the amount of fatty acids.

Free Research Field

自然免疫

Academic Significance and Societal Importance of the Research Achievements

本研究により、mTORC2が脂肪酸のセンサーとしての役割を果たすことがわかった。また、mTORC2が脂肪酸の量をモニターし、十分であれば免疫応答を許容し、不十分であれば免疫応答を禁止し、代謝応答を促進し脂肪酸を作るというスキームを示せた。これは、mTORC2が免疫応答のバランスを制御するオペレーターの役割を果たす「Immuno-metabolism」の新たなモデルとなる。