Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
Ludwig Institute for Cancer Research, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium.
Nat Commun. 2018 May 17;9(1):1981. doi: 10.1038/s41467-018-04366-7.
The tryptophan metabolite kynurenine has critical immunomodulatory properties and can function as an aryl hydrocarbon receptor (AHR) ligand. Here we show that the ability of T cells to transport kynurenine is restricted to cells activated by the T-cell antigen receptor or proinflammatory cytokines. Kynurenine is transported across the T-cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate the AHR is restricted to T cells that express SLC7A5. We use the fluorescence spectral properties of kynurenine to develop a flow cytometry-based assay for rapid, sensitive and quantitative measurement of the kynurenine transport capacity in a single cell. Our findings provide a method to assess the susceptibility of T cells to kynurenine, and a sensitive single cell assay to monitor System L amino acid transport.
色氨酸代谢产物犬尿氨酸具有关键的免疫调节特性，并且可以作为芳烃受体 (AHR) 的配体。在这里，我们表明 T 细胞运输犬尿氨酸的能力仅限于通过 T 细胞抗原受体或促炎细胞因子激活的细胞。犬尿氨酸通过系统 L 转运蛋白 SLC7A5 跨 T 细胞膜转运。因此，犬尿氨酸激活 AHR 的能力仅限于表达 SLC7A5 的 T 细胞。我们利用犬尿氨酸的荧光光谱特性，开发了一种基于流式细胞术的测定法，可快速、灵敏和定量地测量单个细胞中的犬尿氨酸转运能力。我们的发现为评估 T 细胞对犬尿氨酸的敏感性提供了一种方法，并提供了一种灵敏的单细胞测定法来监测系统 L 氨基酸转运。
