Single cell analysis of kynurenine and System L amino acid transport in T cells

Nature Communications
Linda V SinclairDoreen A Cantrell

Abstract

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.

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Citations

Jul 6, 2020·International Immunology·Alok Kumar, Kenji Chamoto
Sep 7, 2019·Journal of Translational Medicine·Hui ZhaoYing-Yong Zhao
Oct 17, 2019·Frontiers in Immunology·Iñigo TerrénFrancisco Borrego
Oct 9, 2019·Nature Immunology·Andrew J M HowdenDoreen A Cantrell
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Methods Mentioned

BETA
flow cytometry
transgenic
xenograft
PCR

Software Mentioned

TreeStar
DIVA
GraphPad Prism
GraphPad
FACSuite
FlowJo

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