The nuclear lamina regulates T-cell senescence via altering chromatin structure

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15728
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Ehime University
• Principal Investigator: Suzuki Junpei 愛媛大学, 医学系研究科, 助教 (20734239)
• Research Collaborator: Yasukawa Masaki ; Yamashita Masakatsu
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: T細胞老化 / T細胞機能 / Lamin A / ファルネシル化

Outline of Final Research Achievements

The lamin A is type V intermediate filament protein that is component of nuclear lamina. We analyzed the effect of Lamin A/C on T-cell senescence and functions, and found that Lamin A/C suppressed the induction of T-cell senescence through regulating mTORC1 activity and glycolysis. The induction of senescent T cells was partially inhibited by farnesyltransferase inhibitors (FTI). Furthermore, Th2 differentiation was induced in Lamin A/C deficient CD4 T cells, and the enhancement of Th2 differentiation in Lamin A/C deficient CD4 T cells was inhibited by FTI treatment.
These results suggest that T-cell senescence and function are partially regulated by Lamin A/C expression or modification.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本申請研究によりLamin A/Cが、mTORC1活性や細胞内エネルギー代謝を介してT細胞老化やTh2細胞分化を制御する可能性を示した。免疫システムの老化(免疫老化)は加齢関連疾患の発症と密接に関わる。本研究では、ファルネシル転移酵素阻害剤が、T細胞老化を部分的に回復させる知見を得た。これらのことから、Lamin A/Cの発現制御や修飾調節を基盤とした、免疫老化に伴う加齢関連疾患の発症予防や新規治療法の開発が行える可能性が示された。