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Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2018-Dec-06 , DOI: 10.1038/s41385-018-0111-7
Wenkai Ren 1, 2, 3 , Yuexia Liao 2, 4 , Xueyan Ding 2 , Ye Jiang 2, 4 , Jiameng Yan 3 , Yaoyao Xia 3 , Bie Tan 3 , Zhijie Lin 2 , Jielin Duan 5 , Xinming Jia 5 , Guan Yang 1 , Jinping Deng 1 , Congrui Zhu 6 , Philip R Hardwidge 6 , Junxia Li 7 , Guoqiang Zhu 2 , Yulong Yin 1, 3, 7
Affiliation  

The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic signatures, such as the GABA shunt pathway, as compared to naïve T cells. GAT-2 deficiency had little effect on the metabolic signature in naïve T cells, but impaired the GABA uptake and GABA shunt pathway in Th17 cells. GAT-2 deficiency had little effect on T cell development and peripheral T cell homeostasis; however, its deficiency promoted Th17 cell differentiation in vitro. Mechanistically, GAT-2 deficiency promoted differentiation of Th17 cells through activation of GABA-mTOR signaling. In a mouse model of intestinal infection and inflammation, GAT-2 deficiency promoted Th17 responses. Collectively, GAT-2 deficiency promotes Th17 cell responses through activation of GABA-mTOR signaling.

中文翻译:

Slc6a13 缺陷促进肠道细菌感染期间的 Th17 反应。

γ-氨基丁酸 (GABA) 能系统决定免疫细胞的激活和功能。本研究旨在探讨 GABA 转运蛋白 (GAT)-2 对 Th17 细胞分化的调控作用。在这里,我们发现与幼稚 T 细胞相比,Th17 细胞显示出更高的 GAT-2 丰度,并且具有明显的细胞代谢特征,例如 GABA 分流通路。GAT-2 缺乏对幼稚 T 细胞的代谢特征几乎​​没有影响,但会损害 Th17 细胞中的 GABA 摄取和 GABA 分流通路。GAT-2 缺陷对 T 细胞发育和外周 T 细胞稳态几乎没有影响;然而,它的缺乏在体外促进了Th17细胞的分化。从机制上讲,GAT-2 缺陷通过激活 GABA-mTOR 信号传导促进 Th17 细胞的分化。在肠道感染和炎症的小鼠模型中,GAT-2 缺陷促进了 Th17 反应。总的来说,GAT-2 缺陷通过激活 GABA-mTOR 信号传导促进 Th17 细胞反应。
更新日期:2019-01-26
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