Evidence map›Paper›PMID 25450716›Full record

ArticleJournal of hepatology2015

Recipient T cell TIM-3 and hepatocyte galectin-9 signalling protects mouse liver transplants against ischemia-reperfusion injury.

Yuanxing Liu, Haofeng Ji, Yu Zhang, Xiuda Shen, Feng Gao, Xiangyi He, Gabriella A Li, Ronald W Busuttil, Vijay K Kuchroo, Jerzy W Kupiec-Weglinski

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

34 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Mouse orthotopic liver transplantation: Challenges, achievements, and applications.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025
    Review
  3. Optimizing the mouse orthotopic liver transplantation model: Learning curve, technical enhancements, and keys to success.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2025
    Article
  4. Novel inflammatory markers in intracerebral hemorrhage: Results from Olink proteomics analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  5. Observational
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023
    Article
  12. Article
  13. Review
  14. Article
  15. The role of Tim-3/Galectin-9 pathway in T-cell function and prognosis of patients with human papilloma virus-associated cervical carcinoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  16. Article
  17. Review
  18. The roles of galectins in hepatic diseases.Journal of molecular histology · 2020
    Review
  19. Review
  20. Article
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 2 countries.

Yuanxing LiuDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA; Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Haofeng JiDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
Yu ZhangDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA; Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Xiuda ShenDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
Feng GaoDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
Xiangyi HeDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Gabriella A LiDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
Ronald W BusuttilDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA.
Vijay K KuchrooCenter for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jerzy W Kupiec-WeglinskiDumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA, USA. Electronic address: jkupiec@mednet.ucla.edu.
University of California, Los Angeles · USZhejiang University · CNBrigham and Women's Hospital · USRuijin Hospital · CN

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
NRF2 - SIRT1 SIGNALING AXIS IN LIVER TRANSPLANT REJUVENATIONR01DK062357 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2003 to 2025
$8.4M
Tim Costimulation in Liver Transplant Ischemia InjuryR01DK102110 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2015 to 2019
$1.7M
NIDDK NIH HHS P30 DK041301NIDDK NIH HHS R01 DK062357NIDDK NIH HHS R01 DK102110
6 · The paper itself

Abstract

BACKGROUND &

aimsBy binding to T cell immunoglobulin mucin-3 (TIM-3) on activated Th1 cells, galectin-9 (Gal-9) negatively regulates Th1-type alloimmunity. Although T cells contribute to hepatic ischemia-reperfusion injury (IRI), it is unknown whether negative T cell-dependent TIM-3 co-stimulation may rescue IR-stressed orthotopic liver transplants from innate immunity-driven inflammation.

methodsWe used wild type (WT) and TIM-3 transgenic (Tg) mice (C57BL/6) as liver donors and recipients in a clinically-relevant model of hepatic cold storage (20 h at 4°C in UW solution) and syngeneic orthotopic liver transplantation (OLT).

resultsOrthotopic liver transplants in WT or TIM-3Tg→TIM-3Tg groups were resistant against IR-stress, evidenced by preserved hepatocellular function (serum ALT levels) and liver architecture (Suzuki's score). In contrast, orthotopic liver transplants in WT or TIM-3Tg→WT groups were susceptible to IRI. TIM-3 induction in circulating CD4+ T cells of the recipient: (1) depressed T-bet/IFN-γ, while amplifying GATA3 and IL-4/IL-10 expression in orthotopic liver transplants; (2) promoted T cell exhaustion (PD-1, LAG-3) phenotype; and (3) depressed neutrophil and macrophage infiltration/function in orthotopic liver transplants. In parallel studies, we documented for the first time that Gal-9, a natural TIM-3 ligand, was produced primarily by and released from IR-stressed hepatocytes, both in vivo and in vitro. Moreover, exogenous recombinant Gal-9 (rGal-9) potentiated liver resistance against IRI by depressing T cell activation and promoting apoptosis of CD4+ T cells.

conclusionsHarnessing TIM-3/Gal-9 signalling at the T cell-hepatocyte interface facilitates homeostasis in IR-stressed orthotopic liver transplants. Enhancing anti-oxidant hepatocyte Gal-9 potentiates liver IR-resistance. Negative regulation by recipient TIM-3+CD4+ cells provides evidence for cytoprotective functions of a discrete T cell subset, which should be spared when applying T cell-targeted immunosuppression in transplant recipients.

Indexed as

Liver TransplantationAdenosineAllopurinolAnimalsApoptosisCell DifferentiationDisease Models, AnimalGalectinsGlutathioneHepatitis A Virus Cellular Receptor 2HepatocytesImmunity, InnateInsulinIn Vitro TechniquesLymphocyte ActivationMacrophagesAdenosineAllopurinolgalectin 9, mouseGalectinsGlutathioneHavcr2 protein, mouseHepatitis A Virus Cellular Receptor 2InsulinOrgan Preservation SolutionsRaffinoseReceptors, VirusUniversity of Wisconsin-lactobionate solutionGalectin-9Innate immunityIschemia-reperfusion injuryLiverOrthotopic liver transplantationTIM-3

Identifiers

PMID25450716
PMCPMC4336640
OpenAlexW2088141661

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Registered trials

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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.