Investigations of the role of glutamine metabolism in the T cell fate determination

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19158
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Ehime University
• Principal Investigator: Kuwahara Makoto 愛媛大学, 医学部附属病院, 助教(病院教員) (00568214)
• Research Collaborator: YAMASHITA Masakatsu
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: T細胞運命決定 / グルタミン代謝 / Th2 / Utx

Outline of Final Research Achievements

We assessed the role of glutamine metabolism in the fate determination of activated T cells in this study. The deprivation of glutamine from culture medium or the pharmacological inhibition of glutamine metabolism suppressed Th2 differentiation and the induction of T cell senescent phenotype in vitro. The administration of alpha-ketoglutarate (α-KG) in cultures under glutamine-deprived conditions restored Th2 differentiation and induced T cell senescent phenotype indicating thatα-KG derived from glutamine is required for Th2 differentiation and induction of T cell senescent phenotype. Furthermore, we found that α-KG-dependent demethylation of the Th2 cytokine gene loci by the H3K27 demethylase Utx is required for the efficient Th2 differentiation. Alpha-KG-dependent histone H3K27 demethylation is also involved in the induction of senescence. These findings reveal the novel role of glutamine metabolism in regulating Th2 differentiation and induction of T cell senescent phenotype.

Free Research Field

免疫学