Regulatory mechanisms of senescence related T cell development by ubiquitination

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Keio University
• Principal Investigator: AKI DAISUKE 慶應義塾大学, 医学部(信濃町), 助教 (50420500)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫老化 / 加齢関連T細胞 / ユビキチン修飾 / 疲弊化 / 抗腫瘍免疫

Outline of Final Research Achievements

Senescence related T cell is a specifically accumulated T cell subset as we age and involved in immunosenescence. To investigate the regulatory mechanisms how senescence related T cells are emerged during aging, we performed in vivo screens to identify ubiquitin related molecules that can regulate senescence related T cell development. We found that a small ubiquitin-related modifier E3 ligase, PIAS1 regulated senescence related T cell induction with promoting T cell exhaustion, which might result in compromised anti-tumor immunity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

翻訳後修飾のT細胞疲弊化への関与は不明であったが、本研究ではユビキチン修飾系がT細胞を介した免疫老化の誘導に関与していることを明らかにした。老化に伴うT細胞の疲弊化は抗腫瘍免疫の低下を招くことから、疲弊化の予防や解除方法の開発は重要である。本研究より得られた知見は、ガン治療戦略の確立に際してユビキチン化のプロセスが、メモリーT細胞における新規の創薬ターゲットとなりうる可能性を示唆している。