Evidence map›Paper›PMID 40588817›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Gamma-Glutamyl Cysteine Ligase Activity as a Proxy for Human T Cell Function and Drug-Induced Immunosuppression.

Francisco Fueyo-González, Carmen Salto-Giron, Mehek Ningoo, Laura Espinar-Barranco, Rafael Salto, Jose Manuel Paredes, Rosario Herranz, Angel Orte, Miguel Fribourg, Juan A González-Vera

Erratum issuedAbstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Francisco Fueyo-GonzálezInstituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, Madrid, 28006, Spain.ORCID https://orcid.org/0000-0001-6837-3928
Carmen Salto-GironNanoscopy-UGR Laboratory. Departamento de Fisicoquímica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, Granada, 18071, Spain.
Mehek NingooDepartment of Medicine, Translational Transplant Research Center, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Laura Espinar-BarrancoDepartment of Medicine, Translational Transplant Research Center, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Rafael SaltoDepartamento de Bioquímica y Biología Molecular II, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, Granada, 18071, Spain.ORCID https://orcid.org/0000-0002-7044-3611
Jose Manuel ParedesNanoscopy-UGR Laboratory. Departamento de Fisicoquímica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, Granada, 18071, Spain.ORCID https://orcid.org/0000-0002-3252-9174
Rosario HerranzInstituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, Madrid, 28006, Spain.ORCID https://orcid.org/0000-0002-0273-2761
Angel OrteNanoscopy-UGR Laboratory. Departamento de Fisicoquímica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, Granada, 18071, Spain.ORCID https://orcid.org/0000-0003-1905-4183
Miguel FribourgDepartment of Medicine, Translational Transplant Research Center, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.ORCID https://orcid.org/0000-0003-1804-8136
Juan A González-VeraNanoscopy-UGR Laboratory. Departamento de Fisicoquímica, Unidad de Excelencia de Química Aplicada a Biomedicina y Medioambiente, Facultad de Farmacia, Universidad de Granada, Campus Cartuja, Granada, 18071, Spain.ORCID https://orcid.org/0000-0002-8199-1330

Funding

Redox homeostasis to capture regulatory T cell heterogeneity in transplantR21AI183028 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CRAVEDI, PAOLO, FRIBOURG, MIGUEL · 2024 to 2025
$458k
Agencia Estatal de Investigación PID2023-148243OB-I00Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía A-FQM-386-UGR20Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía P21_00212NIAID NIH HHS R21 AI183028NIH HHS R21 AI183028
6 · The paper itself

Abstract

T cell effector functions are critical for immune defense, but their dysregulation can cause diseases like immune exhaustion in cancer and loss of tolerance in autoimmunity. Curtailing these functions is essential in therapies such as chimeric antigen receptor T-cell (CAR-T) therapies or organ transplantation to avoid hyperactivation and rejection. A major challenge in the field is the precise, live measurement of T cell function at the single-cell level, limiting the prediction of immune responses, the development of effective immunotherapies, and optimization of immunosuppressive regimens. Gamma-Glutamyl Cysteine Ligase (GCL), the rate-limiting enzyme in glutathione (GSH) synthesis, is essential for T cell function in mice, but its role in human T cells is underexplored. GLed, a novel reversible lanthanide-based GSH sensor is introduced that enables real-time, quantitative measurements of GCL activity at single-cell resolution. The GLed approach distinguishes GSH contributions from GCL and GSR, linking GCL activity directly to human T cell effector functions. Additionally, this reveals previously unknown modulation of GCL activity by immunosuppressive drugs, underscoring GCL as a critical player in T cell function and a potential therapeutic target in immune-related diseases.

Indexed as

Glutamate-Cysteine LigaseImmunosuppression TherapyImmunosuppressive AgentsT-LymphocytesAnimalsGlutathioneHumansMiceGlutamate-Cysteine LigaseGlutathioneImmunosuppressive Agentsglutamate‐cysteine ligaseglutathioneimmunosuppressionlanthanide sensorT cells

Identifiers

PMID40588817
PMCPMC12499489

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.