Evidence map›Paper›PMID 37567451›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2023

Disulfide-HMGB1 signals through TLR4 and TLR9 to induce inflammatory macrophages capable of innate-adaptive crosstalk in human liver transplantation.

Allyson Q Terry, Hidenobu Kojima, Rebecca A Sosa, Fady M Kaldas, Jackson L Chin, Ying Zheng, Bita V Naini, Daisuke Noguchi, Jessica Nevarez-Mejia, Yi-Ping Jin and 5 more

Open access · hybridAbstract 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, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 4% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
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  4. Hepatocyte BDNF Acts as a Novel Immune Checkpoint to Restrain TLR4-Mediated Acute Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  14. Beyond a Biomarker: Investigations of a Proinflammatory Role for Cell-Free DNA in Liver Transplant Ischemia and Reperfusion.Transplant international : official journal of the European Society for Organ Transplantation · 2026
    Article
  15. 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
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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

15 authors at 2 institutions in 1 country.

Allyson Q TerryDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Hidenobu KojimaDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Rebecca A SosaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Fady M KaldasDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jackson L ChinDepartment of Bioengineering, Samueli School of Engineering at UCLA, Los Angeles, California, USA.
Ying ZhengDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Bita V NainiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Daisuke NoguchiDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jessica Nevarez-MejiaDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Yi-Ping JinDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Ronald W BusuttilDivision of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Aaron S MeyerDepartment of Bioengineering, Samueli School of Engineering at UCLA, Los Angeles, California, USA.
David W GjertsonDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Department of Biostatistics, Fielding School of Public Health at UCLA, Los Angeles, California, USA.
Jerzy W Kupiec-WeglinskiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA; Division of Liver and Pancreas Transplantation, Department of Surgery, 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. Electronic address: ereed@mednet.ucla.edu.
University of California, Los Angeles · USSamueli Institute · US

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
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Mapping the effector response space of antibody combinationsU01AI148119 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MEYER, AARON SAMUEL, NIMMERJAHN, FALK · 2020 to 2024
$1.6M
NCI NIH HHS T32 CA009120NIAID NIH HHS P01 AI120944NIAID NIH HHS U01 AI148119NIMHD NIH HHS L60 MD011903
6 · The paper itself

Abstract

Ischemia-reperfusion injury (IRI) during orthotopic liver transplantation (OLT) contributes to graft rejection and poor clinical outcomes. The disulfide form of high mobility group box 1 (diS-HMGB1), an intracellular protein released during OLT-IRI, induces pro-inflammatory macrophages. How diS-HMGB1 differentiates human monocytes into macrophages capable of activating adaptive immunity remains unknown. We investigated if diS-HMGB1 binds toll-like receptor (TLR) 4 and TLR9 to differentiate monocytes into pro-inflammatory macrophages that activate adaptive immunity and promote graft injury and dysfunction. Assessment of 106 clinical liver tissue and longitudinal blood samples revealed that OLT recipients were more likely to experience IRI and graft dysfunction with increased diS-HMGB1 released during reperfusion. Increased diS-HMGB1 concentration also correlated with TLR4/TLR9 activation, polarization of monocytes into pro-inflammatory macrophages, and production of anti-donor antibodies. In vitro, healthy volunteer monocytes stimulated with purified diS-HMGB1 had increased inflammatory cytokine secretion, antigen presentation machinery, and reactive oxygen species production. TLR4 inhibition primarily impeded cytokine/chemokine and costimulatory molecule programs, whereas TLR9 inhibition decreased HLA-DR and reactive oxygen species production. diS-HMGB1-polarized macrophages also showed increased capacity to present antigens and activate T memory cells. In murine OLT, diS-HMGB1 treatment potentiated ischemia-reperfusion-mediated hepatocellular injury, accompanied by increased serum alanine transaminase levels. This translational study identifies the diS-HMGB1/TLR4/TLR9 axis as potential therapeutic targets in OLT-IRI recipients.

Indexed as

HMGB1 ProteinLiver TransplantationReperfusion InjuryAnimalsApoptosisCytokinesHumansLiverMacrophagesMiceMice, Inbred C57BLReactive Oxygen SpeciesToll-Like Receptor 4Toll-Like Receptor 9CytokinesHMGB1 ProteinReactive Oxygen SpeciesTLR4 protein, humanTLR9 protein, humanToll-Like Receptor 4Toll-Like Receptor 9alloimmunitydisulfide-HMGB1ischemia-reperfusion injurypro-inflammatory macrophageTLR activation

Identifiers

PMID37567451
PMCPMC11095628
OpenAlexW4385704155

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.