Metabolomics Analysis of the Effect of GAT-2 Deficiency on Th1 Cells in Mice

The classic neurotransmitter γ-aminobutyric acid (GABA) has been shown to shape the activation and function of immune cells. There are four high-affinity GABA transporters (GATs, including GAT-1, GAT-2, GAT-3, and GAT-4) responsible for the transmembrane transport of GABA in mice. To explore the effect of GAT-2 on type 1 helper T (Th1) cells, naïve CD4⁺ T cells were isolated from splenocytes of GAT-2 knockout (KO) and wild-type (WT) mice and cultured for Th1 cell differentiation, and then, metabolomics analysis of Th1 cells was performed via gas chromatography coupled to time-of-flight mass spectrometry added with multivariate analyses. Based on the variable importance projection value > 1 and P < 0.05, a total of nine differentially expressed metabolites (DEMs) were identified between WT and KO. Then, DEMs were mapped to the KEGG database, and five metabolic pathways were significantly enriched, including the cysteine and methionine metabolism, the riboflavin metabolism, the purine metabolism, the glycerolipid metabolism, and the glycerophospholipid metabolism. Collectively, our metabolomics analysis revealed that deficiency of GAT-2 influenced the metabolomics profile of Th1 cells, which will provide insights into T cell response to GAT-2 deficiency in mice. Data are available via MetaboLights with identifier MTBLS3358.