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

Linda Sinclair (Lead / Corresponding author), Damien Neyens, George Ramsay, Peter Taylor, Doreen Cantrell (Lead / Corresponding author)

Research output: Contribution to journalArticle

6 Citations (Scopus)
61 Downloads (Pure)

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 pro-inflammatory cytokines. Kynurenine is transported across the T cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate 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 (2018)
Number of pages11
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 17 May 2018

Fingerprint

Amino Acid Transport System L
Single-Cell Analysis
Kynurenine
T-cells
Systems Analysis
amino acids
T-Lymphocytes
Amino Acids
Large Neutral Amino Acid-Transporter 1
cells
hydrocarbons
Aryl Hydrocarbon Receptors
transporter
cytometry
metabolites
tryptophan
antigens
Assays
Flow cytometry
magnetic permeability

Keywords

  • Biochemistry
  • Cell biology
  • Flow cytometry
  • T cells

Cite this

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title = "Single cell analysis of kynurenine and System L amino acid transport in T cells",
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 pro-inflammatory cytokines. Kynurenine is transported across the T cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate 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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Single cell analysis of kynurenine and System L amino acid transport in T cells. / Sinclair, Linda (Lead / Corresponding author); Neyens, Damien ; Ramsay, George; Taylor, Peter; Cantrell, Doreen (Lead / Corresponding author).

In: Nature Communications, Vol. 9, No. 1, 1981 (2018), 17.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Single cell analysis of kynurenine and System L amino acid transport in T cells

AU - Sinclair, Linda

AU - Neyens, Damien

AU - Ramsay, George

AU - Taylor, Peter

AU - Cantrell, Doreen

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PY - 2018/5/17

Y1 - 2018/5/17

N2 - 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 pro-inflammatory cytokines. Kynurenine is transported across the T cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate 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.

AB - 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 pro-inflammatory cytokines. Kynurenine is transported across the T cell membrane by the System L transporter SLC7A5. Accordingly, the ability of kynurenine to activate 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.

KW - Biochemistry

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