Integrated regulation of T cell signaling and differentiation by glutamine

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03504
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Ehime University
• Principal Investigator: Yamashita Masakatsu 愛媛大学, 医学系研究科, 教授 (00311605)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: T細胞 / グルタミン / シグナル伝達 / 解糖系

Outline of Final Research Achievements

The increased activity of the glycolytic system upon T cell antigen recognition is required for activation of glutamine metabolism, and glutamine maintains activation of the glycolytic system via sustained activity of mTOR. In other words, it was suggested that the glycolytic system and glutamine metabolism may form a feed-forward loop to prolong signals via TCR and cytokine receptors and maintain T cell activation. These results indicate that glycolytic activation in T cells upon antigen recognition is essential for the induction of normal T cell-dependent immune responses and is a therapeutic target for the treatment of immunological diseases. We also found that glutamine may regulate T cellular senescence via modulation of autophagy.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

グルタミンが活性化T細胞における解糖系、シグナル伝達の維持に必要であることが明らかにするとともに、活性化T細胞におけるグルタミン（代謝）がオートファジーの調節を介してT細胞老化を制御している可能性を新たに見出したことが、今回の研究成果の学樹的意義である。また、グルタミン流入阻害やT細胞解糖系酵素阻害が免疫疾患の治療標的になることを示したことは、免疫抑制による疾患治療の新しい選択肢を提示したという点において社会的なインパクトは大きい。