Evidence map›Paper›PMID 27594594›Full record

ArticleJournal of immunological methods2016

Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes.

Peter J Siska, Bumki Kim, Xiangming Ji, Megan D Hoeksema, Pierre P Massion, Kathryn E Beckermann, Jianli Wu, Jen-Tsan Chi, Jiyong Hong, Jeffrey C Rathmell

Open access · greenAbstract read
In one paragraph

Article in Journal of immunological methods, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Inflammatory CD4iScience · 2026
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  7. Review
  8. Review
  9. Review
  10. Review
  11. Immunometabolic Rewiring: A Tale of Macronutrients and Macrophages.Results and problems in cell differentiation · 2024
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. PET Imaging of System xJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
    Article
  19. Review
  20. Systems-based approaches to study immunometabolism.Cellular & molecular immunology · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Peter J SiskaDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37323, United States. Electronic address: peter.siska@vanderbilt.edu.
Bumki KimDepartment of Chemistry, Duke University, Durham, NC 27708, United States.
Xiangming JiDivision of Allergy, Pulmonary and Critical Care Medicine, Thoracic Oncology Center, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37323, United States.
Megan D HoeksemaDivision of Allergy, Pulmonary and Critical Care Medicine, Thoracic Oncology Center, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37323, United States.
Pierre P MassionDivision of Allergy, Pulmonary and Critical Care Medicine, Thoracic Oncology Center, Vanderbilt Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37323, United States.
Kathryn E BeckermannDivision of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37323, United States.
Jianli WuMolecular Genetics and Microbiology, Duke University Medical Center Durham, NC 27710, United States.
Jen-Tsan ChiMolecular Genetics and Microbiology, Duke University Medical Center Durham, NC 27710, United States.
Jiyong HongDepartment of Chemistry, Duke University, Durham, NC 27708, United States.
Jeffrey C RathmellDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN 37323, United States.
Vanderbilt University · USVanderbilt University Medical Center · USDuke Medical Center · USDuke University · US

Funding

Exploiting metabolic vulnerabilities of CD4 T cell subsets to control inflammatory diseaseR01DK105550 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jeffrey C Rathmell · 2015 to 2026
$4.7M
NIDDK NIH HHS R01 DK105550
6 · The paper itself

Abstract

T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide sufficient and necessary intracellular metabolites, uptake of extracellular nutrients increases sharply with metabolic re-programming. One result of increased metabolic activity can be reactive oxygen species (ROS), which can be toxic when accumulated in excess. Uptake of cystine allows accumulation of cysteine that is necessary for glutathione synthesis and ROS detoxification. Cystine uptake is required for T cell activation and function but measurements based on radioactive labeling do not allow analysis on single cell level. Here we show the critical role for cystine uptake in T cells using a method for measurement of cystine uptake using a novel CystineFITC probe. T cell receptor stimulation lead to upregulation of the cystine transporter xCT (SLC7a11) and increased cystine uptake in CD4+ and CD8+ human T cells. Similarly, lipopolysaccharide stimulation increased cystine uptake in human B cells. The CystineFITC probe was not toxic and could be metabolized to prevent cystine starvation induced cell death. Furthermore, blockade of xCT or competition with natural cystine decreased uptake of CystineFITC. CystineFITC is thus a versatile tool that allows measurement of cystine uptake on single cell level and shows the critical role for cystine uptake for T cell ROS regulation and activation.

Indexed as

Lymphocyte ActivationAmino Acid Transport System y+B-LymphocytesCell Line, TumorCellular ReprogrammingCystineFlow CytometryFluorescein-5-isothiocyanateFluorescenceFluorescent DyesGlutathioneHumansMicroscopy, FluorescenceReactive Oxygen SpeciesReceptors, Antigen, T-CellSignal TransductionAmino Acid Transport System y+CystineFluorescein-5-isothiocyanateFluorescent DyesGlutathioneReactive Oxygen SpeciesReceptors, Antigen, T-CellSLC7A11 protein, humanCystineCystineFITCMetabolismReactive oxygen species (ROS)T cellsxCT

Identifiers

PMID27594594
PMCPMC5065394
OpenAlexW2507504115

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.