Evidence map›Paper›PMID 39736469›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2025

Group 1 innate lymphoid cells protect liver transplants from ischemia-reperfusion injury via an interferon gamma-mediated pathway.

Hidenobu Kojima, Thomas A Morinelli, Yue Wang, Jackson L Chin, Aaron S Meyer, Yi-Chu Kao, Kentaro Kadono, Siyuan Yao, Taylor Torgerson, Kenneth J Dery and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

17 authors.

Hidenobu KojimaThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Thomas A MorinelliDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Yue WangDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Jackson L ChinDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA.
Aaron S MeyerDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA.
Yi-Chu KaoDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Kentaro KadonoThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Siyuan YaoThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Taylor TorgersonThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kenneth J DeryThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Adil BhatDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Elaine F ReedDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Fady M KaldasThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Dirk J van der WindtDepartment of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.
Douglas G FarmerThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jerzy W Kupiec-WeglinskiThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Yuan ZhaiThe Dumont-UCLA Transplantation Center, Department of Surgery, Division of Liver and Pancreas Transplantation, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: zhaiy@musc.edu.

Funding

Regulation of Innate Immune Responses by Alloimmunity in Liver Ischemia-Reperfusion InjuryP01AI120944 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ELAINE F REED · 2017 to 2026
$20.0M
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
TIM-3 Negative Costimulation Signaling at the Innate-Adaptive Immune interface in Liver Transplant Ischemia-Reperfusion InjuryR01DK107533 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KUPIEC-WEGLINSKI, JERZY W · 2016 to 2020
$1.7M
Glycogen Synthase Kinase 3 beta in liver ischemia reperfusion injuryR01DK119338 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZHAI, YUAN · 2020 to 2023
$1.4M
NIAID NIH HHS P01 AI120944NIDDK NIH HHS R01 DK062357NIDDK NIH HHS R01 DK102110NIDDK NIH HHS R01 DK107533NIDDK NIH HHS R01 DK119338
6 · The paper itself

Abstract

As important immune regulatory cells, whether innate lymphoid cells (ILCs) are involved in liver transplantation (LT) remains unclear. In a murine orthotopic LT model, we dissected roles of ILCs in liver ischemia-reperfusion injury (IRI). Wild-type (WT) grafts suffered significantly higher IRI in Rag2-γc double knockout (DKO) than Rag2 knockout (KO) recipients, in association with downregulation of group 1 ILCs genes, including interferon gamma. Antibody-mediated ILC depletion or interferon gamma neutralization in Rag2 KO recipients increased, while interferon gamma treatment in DKO recipients reduced, liver graft injuries. At the donor side, grafts from DKO mice or anti-NK1.1-treated WT mice suffered significantly higher IRI, while grafts treated with interferon gamma during cold preservation decreased IRI. Thus, both recipient and donor group 1 ILCs protect liver grafts from IRI. Low-dose interferon gamma upregulated c-FLIP expression in vitro and in vivo and protected hepatocytes from inflammatory cell death. In human liver graft biopsies, single-cell RNA-sequencing analysis revealed group 1 ILCs produce interferon gamma. The c-FLIP levels were positively correlated with interferon gamma in pretransplant biopsies. Grafts with higher c-FLIP were associated with lower caspase-8 activation, IRI gradings, and frequency of early allograft dysfunction post-LT. Our study reveals a novel interferon gamma-mediated cytoprotective role of group 1 ILCs in LT.

Indexed as

Graft RejectionImmunity, InnateInterferon-gammaLiver TransplantationLymphocytesReperfusion InjuryAnimalsGraft SurvivalHumansMaleMiceMice, Inbred C57BLMice, KnockoutInterferon-gammaacute liver injuryapoptosisinnate lymphoid cellinterferon gammaliver transplantation

Identifiers

PMID39736469
PMCPMC12043423

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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.