2021 Fiscal Year Final Research Report

Regulation of memory T cell generation and function by fatty acid metabolism

Research Project

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Project/Area Number	20K20383
Project/Area Number (Other)	18H05375 (2018-2019)
Research Category	Grant-in-Aid for Challenging Research (Pioneering)
Allocation Type	Multi-year Fund (2020) Single-year Grants (2018-2019)
Review Section	Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research Institution	Chiba University
Principal Investigator	Nakayama Toshinori 千葉大学, その他部局等, 学長 (50237468)
Project Period (FY)	2018-06-29 – 2022-03-31
Keywords	免疫記憶 / 脂肪酸代謝 / 記憶T細胞 / 喘息
Outline of Final Research Achievements	In pathogenic memory Th2 (Tpath2) cells, which are involved in chronic inflammation such as asthma, fatty acid metabolism pathway play an important role. We focused on two molecules that control fatty acid metabolism in Tpath2 cells: Stearoyl-CoA desaturase 2 (Scd2) and acetyl-CoA carboxylase 1 (ACC1). In the present study, we found that Scd2 and ACC1 expressed in Tpath2 cells regulate immune responses via controlling fatty acid metabolites. These findings have been reported in two separated papers. In addition, we published several other papers and had active discussions on the pathogenic T cells at domestic and international congresses. Although it is still debatable whether fatty acid metabolism could be potential therapeutic target, our findings will be helpful for better understanding of the fatty acid metabolism in the pathogenic T cells and chronic inflammation.
Free Research Field	免疫学、アレルギー学
Academic Significance and Societal Importance of the Research Achievements	本研究では、総説等で単純化されすぎたモデルが提唱されているT細胞での代謝経路に焦点を当て、「細胞内代謝経路を操作することで免疫細胞の機能を制御できないか？」という仮説の検証を試みた。その結果、従来の単純化モデルでは注目されなかった脂肪酸代謝と記憶T細胞の関連を示唆する、T細胞の代謝モデルを書き換える免疫学上重要な知見が得られた。また、脂肪酸代謝を人工的に操作することで、慢性炎症に関与する病原性記憶T細胞を抑制可能というデータも得られ、「免疫記憶を代謝で制御する」という開始当初の目標に向けて一歩前進し、喘息などの慢性難治性炎症疾患の治療法開発等、将来的に大きな社会的意義をもたらすと考えられる。