College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
Front Immunol. 2021 Jun 2;12:667136. doi: 10.3389/fimmu.2021.667136. eCollection 2021.
The neurotransmitter γ-aminobutyric acid (GABA) is known to affect the activation and function of immune cells. This study investigated the role of GABA transporter (GAT)-2 in the differentiation of type 1 helper T (Th1) cells. Naïve CD4 T cells isolated from splenocytes of GAT-2 knockout (KO) and wild-type (WT) mice were cultured; Th1 cell differentiation was induced and transcriptome and bioinformatics analyses were carried out. We found that GAT-2 deficiency promoted the differentiation of naïve T cells into Th1 cells. RNA sequencing revealed 2984 differentially expressed genes including 1616 that were up-regulated and 1368 that were down-regulated in GAT-2 KO cells compared to WT cells, which were associated with 950 enriched Gene Ontology terms and 33 enriched Kyoto Encyclopedia of Genes and Genomes pathways. Notably, 4 signal transduction pathways (hypoxia-inducible factor [HIF]-1, Hippo, phospholipase D, and Janus kinase [JAK]/signal transducer and activator of transcription [STAT]) and one metabolic pathway (glycolysis/gluconeogenesis) were significantly enriched by GAT-2 deficiency, suggesting that these pathways mediate the effect of GABA on T cell differentiation. Our results provide evidence for the immunomodulatory function of GABA signaling in T cell-mediated immunity and can guide future studies on the etiology and management of autoimmune diseases.
神经递质 γ-氨基丁酸（GABA）已知会影响免疫细胞的激活和功能。本研究探讨了 GABA 转运蛋白（GAT）-2 在 1 型辅助 T（Th1）细胞分化中的作用。从 GAT-2 敲除（KO）和野生型（WT）小鼠脾细胞中分离出幼稚 CD4 T 细胞进行培养；诱导 Th1 细胞分化，并进行转录组和生物信息学分析。我们发现 GAT-2 缺乏促进了幼稚 T 细胞向 Th1 细胞的分化。RNA 测序显示，与 WT 细胞相比，GAT-2 KO 细胞中有 2984 个差异表达基因，包括 1616 个上调基因和 1368 个下调基因，这些基因与 950 个富集的基因本体术语和 33 个富集的京都基因与基因组百科全书途径相关。值得注意的是，4 个信号转导途径（缺氧诱导因子 [HIF]-1、 Hippo、磷脂酶 D 和 Janus 激酶 [JAK]/信号转导和转录激活因子 [STAT]）和一个代谢途径（糖酵解/糖异生）被 GAT-2 缺乏显著富集，表明这些途径介导了 GABA 对 T 细胞分化的影响。我们的研究结果为 GABA 信号在 T 细胞介导的免疫中的免疫调节功能提供了证据，并为自身免疫性疾病的病因和治疗提供了指导。
