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

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

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 ).

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

KW - Cell biology

KW - Flow cytometry

KW - T cells

U2 - 10.1038/s41467-018-04366-7

DO - 10.1038/s41467-018-04366-7

M3 - Article

C2 - 29773791

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1981 (2018)

ER -