Mechanism of JunB function in the differentiation of CD8+ T cells.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16293
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Okinawa Institute of Science and Technology Graduate University
• Principal Investigator: Taira Naoyuki 沖縄科学技術大学院大学, 免疫シグナルユニット, ポストドクトラルスカラー (40813621)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: CD8T細胞 / 転写因子 / JunB

Outline of Final Research Achievements

The importance of AP-1 transcription factors in T cell differentiation has been widely reported. However, the function of JunB, a type of AP-1 transcription factor, in CD8+ T cell differentiation is largely unknown. We investigated the role of JunB in effector CD8+ T cell differentiation. We found that JunB expression occurred 4 days after infection with LM-OVA, while downregulated 7 days after infection. Importantly, the accumulation of effector CD8+ T cells did not occur with the loss of JunB. This result is attributed to the high expression of Bim and activation of caspase-3 in JunB-deficient cells. Next, Bulk RNA-seq analysis was performed to investigate the effects of JunB other than cell death under cell culture conditions. Interestingly, we found that increased expression of PD-1 and Tim-3, which are involved in exhaustion in JunB deficient cell, suggesting that JunB may regulate not only effector cell survival but also exhaustion.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

今回の結果から、CD8T細胞におけるエフェクター細胞分化においてのJunBタンパク質の役割を解明できた。JunBを欠損することでエフェクターCD8T細胞の蓄積がほとんど起こらないことから、JunBの存在はCD8T細胞が活性化し、外来抗原を除去するために非常に重要であり獲得免疫システムにおいて核となるタンパク質であると考えられた。さらにPD-1やTim-3等の疲弊化マーカーの発現に関連する可能性も示唆されたことから、今後がん免疫療法で着目されているエフェクターCD8T細胞の疲弊化を解除するための研究に繋がり、効果的ながん免疫療法の発展へ期待できる。