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

Linda V. Sinclair*, Damien Neyens, George Ramsay, Peter M. Taylor, Doreen A. Cantrell

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)
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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.

Original languageEnglish
Article number1981
Number of pages11
JournalNature Communications
Volume9
Early online date17 May 2018
DOIs
Publication statusPublished - 17 May 2018

Bibliographical note

Acknowledgements
We thank Cantrell group members for their critical discussion of the data, the Biological Resources unit, Sarah Thomson (for rLM work) and the Flow Cytometry facility (A. Whigham and R. Clarke) at the University of Dundee. This work was supported by the Wellcome Trust (Principal Research Fellowship to D.A.C. 097418/Z/11/Z and 205023/Z/16/Z, and Wellcome Trust Equipment Award 202950/Z/16/Z).

Keywords

  • Biochemistry
  • Cell biology
  • Flow Cytometry
  • T cells

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