Evidence map›Paper›PMID 39128812›Full record

ArticleTransplant immunology2024

Single cell RNA-sequencing identifies the effect of Normothermic ex vivo liver perfusion on liver-resident T cells.

David Al-Adra, Ruoxin Lan, Heather Jennings, Kristin N Weinstein, Yongjun Liu, Bret Verhoven, Weifeng Zeng, Grace Heise, Mia Levitsky, Peter Chlebeck and 1 more

Abstract read
In one paragraph

Article in Transplant immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

11 authors.

David Al-AdraDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. Electronic address: aladra@wisc.edu.
Ruoxin LanDepartment of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
Heather JenningsDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Kristin N WeinsteinDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Yongjun LiuDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, USA.
Bret VerhovenDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Weifeng ZengDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Grace HeiseDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Mia LevitskyDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Peter ChlebeckDepartment of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Yao-Zhong LiuDepartment of Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
Targeting Donor Regulatory Dendritic Cells During Normothermic Ex Vivo Liver Perfusion to Overcome Rejection after Liver TransplantK08AI155816 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI AL-ADRA, DAVID PETER · 2021 to 2025
$894k
NCI NIH HHS P30 CA014520NIAID NIH HHS K08 AI155816
6 · The paper itself

Abstract

backgroundNormothermic ex vivo liver perfusion (NEVLP) is an exciting strategy to preserve livers prior to transplant, however, the effects of NEVLP on the phenotype of tissue-resident immune cells is largely unknown. The presence of tissue-resident memory T cells (TRM) in the liver may protect against acute rejection and decrease allograft dysfunction. Therefore, we investigated the effects of NEVLP on liver TRMs and assessed the ability of anti-inflammatory cytokines to reduce TRM activation during NEVLP.

methodsRat livers underwent NEVLP with or without the addition of IL-10 and TGF-β. Naïve and cold storage livers served as controls. Following preservation, TRM T cell gene expression profiles were assessed through single cell RNA sequencing (scRNA-seq). Differential gene expression analysis was performed with Wilcoxon rank sum test to identify differentially expressed genes (DEGs) associated with a specific treatment group. Using the online Database for Annotation, Visualization and Integrated Discovery (DAVID), gene set enrichment was then conducted with Fisher's exact test on DEGs to highlight differentially regulated pathways and functional terms associated with treatment groups.

resultsThrough scRNA-seq analysis, an atlas of liver-resident memory T cell subsets was created for all livers. TRM T cells could be identified in all livers, and through scRNA-seq, DEG was identified with Wilcoxon rank sum test at FDR < 0.05. Based on the gene set enrichment analysis of DEGs using Fisher's exact test, NEVLP is associated with downregulation of multiple gene enrichment pathways associated with surface proteins. Furthermore, NEVLP with anti-inflammatory cytokines was associated with down regulation of 52 genes in TRM T cells when compared to NEVLP alone (FDR <0.05), most of which are pro-inflammatory.

conclusionThis is the first study to create an atlas of liver TRM T cells in the rat liver undergoing NEVLP and demonstrate the effects of NEVLP on liver TRM T cells at the single cell gene expression level.

Indexed as

LiverLiver TransplantationPerfusionSequence Analysis, RNASingle-Cell AnalysisAnimalsGraft RejectionMaleMemory T CellsOrgan PreservationRatsRats, Inbred LewLiver-resident cellsLiver transplantationMemory T cellNormothermic perfusion

Identifiers

PMID39128812
PMCPMC11387148

What OpenQuestion holds

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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.