Identification of functional lipids that control Th17/Treg balance in an obese environment

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03455
• 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: Kazusa DNA Research Institute
• Principal Investigator: ENDO YUSUKE 公益財団法人かずさDNA研究所, 先端研究開発部, 室長 (80612192)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 脂質代謝 / Th17 / Treg / 肥満 / 免疫疾患 / ACC1

Outline of Final Research Achievements

This study has established that Th17 cells and Tregs are differently oriented in lipid metabolism through the identification of the responsible lipid LPE (1-18:1) and metabolic enzyme cascade that controls RORgt activity in Th17 cells, as well as the role of the Acsbg1 enzyme in regulating tissue-resident Treg homeostasis and environmental lipid intake. We were able to establish that Th17 cells and Tregs differ in their orientation of lipid metabolism. We have summarized these results in a number of publications, including in Science Immunology and Cell Reports. Currently, we are continuing our research and conducting more detailed analysis of how specific qualities are responsible for each cellular function by generating point mutant mice.

Free Research Field

免疫代謝

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、T細胞サブセットは異なる代謝志向性を示すことが明らかとなった。これは、代謝を調節することにより免疫機能を特異的にコントロールできることを意味している。究極的に言うと、自己免疫疾患病態をわずらっている患者に対してはTh17細胞を抑制し、Tregを上昇させる方向へと脂質代謝を制御し、逆にがん患者では、Tregを抑制し、CTL活性を上げる方向へと代謝を調節することで副反応を大きく減らした状態での層別化治療を行うことにつなげられる。また、脂質を含む代謝物は生命の根源となるものであり、食事からの摂取をコントロールすることで予防としての作用もあるため、その波及効果は極めて大きい。