Evidence map›Paper›PMID 26489460›Full record

ArticleCell reports2015

Preventing Allograft Rejection by Targeting Immune Metabolism.

Chen-Fang Lee, Ying-Chun Lo, Chih-Hsien Cheng, Georg J Furtmüller, Byoungchol Oh, Vinicius Andrade-Oliveira, Ajit G Thomas, Caitlyn E Bowman, Barbara S Slusher, Michael J Wolfgang and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
15.9field-weighted citation impact, top 1% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 172 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Suppression of cardiac allograft vasculopathy by a macrophage efferocytosis receptor.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Mitochondrial Regulation of CD8⁺ T Cells: Mechanisms and Therapeutic Modulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  12. Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  13. Article
  14. Review
  15. Article
  16. Aberrant glucose metabolism drives dysfunction of CD4Central-European journal of immunology · 2025
    Article
  17. Car T Cells in Solid Tumors: Overcoming Obstacles.International journal of molecular sciences · 2024
    Review
  18. Engineering metabolism to modulate immunity.Advanced drug delivery reviews · 2024
    Review
  19. Glycolysis Changes in Alloreactive Memory B Cells in Highly Sensitized Kidney Transplant Recipients Undergoing Desensitization Therapy.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Article
  20. Harnessing Immune Cell Metabolism to Modulate Alloresponse in Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024
    Review

62 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 2 countries.

Chen-Fang LeeSidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Chang-Gung Transplantation Institute, Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 333, Taiwan.
Ying-Chun LoSidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Chih-Hsien ChengSidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Chang-Gung Transplantation Institute, Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 333, Taiwan.
Georg J FurtmüllerVascularized Composite Allotransplantation Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Byoungchol OhVascularized Composite Allotransplantation Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Vinicius Andrade-OliveiraSidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Ajit G ThomasDepartment of Neurology and Brain Science Institute, NeuroTranslational Drug Discovery Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Caitlyn E BowmanDepartment of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Barbara S SlusherDepartment of Neurology and Brain Science Institute, NeuroTranslational Drug Discovery Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Michael J WolfgangDepartment of Biological Chemistry, Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Gerald BrandacherVascularized Composite Allotransplantation Laboratory, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Jonathan D PowellSidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: poweljo@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USChang Gung Memorial Hospital · TWSidney Kimmel Comprehensive Cancer Center · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
A central role for mTOR in Determining T Cell Activation versus ToleranceR01AI077610 · NIAID · JOHNS HOPKINS UNIVERSITY · PI POWELL, JONATHAN D · 2009 to 2019
$4.0M
Regulation of Neuronal Lipid Homeostasis By ThioesterasesR01NS072241 · NINDS · JOHNS HOPKINS UNIVERSITY · PI WOLFGANG, MICHAEL J. · 2011 to 2020
$4.0M
Transplantation tolerance and immune function following mTOR inhibition.R01AI091481 · NIAID · JOHNS HOPKINS UNIVERSITY · PI POWELL, JONATHAN D · 2010 to 2013
$1.6M
NIAID NIH HHS R01 AI077610NIAID NIH HHS R01AI077610NIAID NIH HHS R01 AI091481NIGMS NIH HHS T32 GM007445NINDS NIH HHS R01 NS072241
6 · The paper itself

Abstract

Upon antigen recognition and co-stimulation, T lymphocytes upregulate the metabolic machinery necessary to proliferate and sustain effector function. This metabolic reprogramming in T cells regulates T cell activation and differentiation but is not just a consequence of antigen recognition. Although such metabolic reprogramming promotes the differentiation and function of T effector cells, the differentiation of regulatory T cells employs different metabolic reprogramming. Therefore, we hypothesized that inhibition of glycolysis and glutamine metabolism might prevent graft rejection by inhibiting effector generation and function and promoting regulatory T cell generation. We devised an anti-rejection regimen involving the glycolytic inhibitor 2-deoxyglucose (2-DG), the anti-type II diabetes drug metformin, and the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON). Using this triple-drug regimen, we were able to prevent or delay graft rejection in fully mismatched skin and heart allograft transplantation models.

Indexed as

AllograftsAnimalsCD8-Positive T-LymphocytesCells, CulturedDeoxyglucoseDiazooxonorleucineEnzyme-Linked Immunosorbent AssayFlow CytometryGlutamineGlycolysisGraft RejectionHeart TransplantationMetforminMiceMice, Inbred BALB CMice, TransgenicDeoxyglucoseDiazooxonorleucineGlutamineMetformin

Identifiers

PMID26489460
PMCPMC4626381
OpenAlexW1897687685

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.