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

Linda Sinclair; Damien  Neyens; George Ramsay; Peter Taylor; Doreen Cantrell

doi:10.1038/s41467-018-04366-7

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 journal › Article › peer-review

120 Citations (Scopus)

192 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 language	English
Article number	1981 (2018)
Number of pages	11
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04366-7
Publication status	Published - 17 May 2018

Keywords

Biochemistry
Cell biology
Flow cytometry
T cells

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry,Genetics and Molecular Biology

Access to Document

10.1038/s41467-018-04366-7Licence: CC BY

Final Published VersionFinal published version, 1.3 MBLicence: CC BY

Serine Kinase Pathways that Determine T Lymphocyte Activation and Cell Fate Choices (Principal Research Fellowship renewal)
Cantrell, D. (Investigator)
1/10/12 → 1/10/24
Project: Research

Cantrell, Doreen
- Cell Signalling and Immunology - Wellcome Trust Principal Research Fellow of Immunology
Person: Academic

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.",

keywords = "Biochemistry, Cell biology, Flow cytometry, T cells",

author = "Linda Sinclair and Damien Neyens and George Ramsay and Peter Taylor and Doreen Cantrell",

note = "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 ).",

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AU - Sinclair, Linda

AU - Neyens, Damien

AU - Ramsay, George

AU - Taylor, Peter

AU - Cantrell, Doreen

N1 - 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 ).

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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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KW - Flow cytometry

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JO - Nature Communications

JF - Nature Communications

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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Projects

Serine Kinase Pathways that Determine T Lymphocyte Activation and Cell Fate Choices (Principal Research Fellowship renewal)

Profiles

Cantrell, Doreen

Cite this