Exploring mechanism and functional significance of T-cell mitochondrial dysfunction induced by thymic involution

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K23862
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Kyoto University
• Principal Investigator: JO Norihide 京都大学, 医学研究科, 特定助教 (50849552)
• Project Period (FY): 2019-08-30 – 2023-03-31
• Keywords: T細胞 / ミトコンドリア / 胸腺退縮 / 恒常性増殖 / 代謝 / MDR1

Outline of Final Research Achievements

This study started based on preliminary results of decreased MitoTracker staining in T cells from adult-thymectomized mice (ATx). However, additional analyzes such as electron microscopy failed to demonstrate mitochondrial dysfunction in ATx-derived T cells. While searching for responsible factors, we found that the MDR1 gene was highly expressed in ATx-derived T cells, and an MDR1 inhibitor canceled the reduced MitoTracker staining of ATx-derived T cells. These results disproved the initial hypothesis, but newly suggested the importance of MDR1 in T-cell senescence. T cells derived from MDR1-deficient mice showed decreased survival in cytokine-free cultures.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

獲得免疫の中心的役割を担うT細胞の産生臓器「胸腺」は思春期以降退縮する。しかし、末梢性T細胞が緩やかに自己複製・増殖することでT細胞産生低下を代償するために、高齢になっても全身のT細胞プールは維持される。申請者はこのT細胞の生存・維持において重要な役割を果たす分子機構について研究を実施した。研究期間終了までに最終的な結論を示すことはできなかったが、今後も継続して研究を進展させていくことで、T細胞の生存・維持だけでなく、癌や感染症などの加齢関連疾患の原因となる「T細胞老化」に新たな知見を加えると期待する。