Evidence map›Paper›PMID 41334456›Full record

ArticleJHEP reports : innovation in hepatology2025

Transcriptome of monocytes from liver, brain and bone marrow reveals organ-specific features in aging and alcohol misuse.

Martí Ortega-Ribera, Radhika Joshi, Sergi Guixé-Muntet, Veronika Brezani, Prashanth Thevkar Nagesh, Viliam Brezani, Arman Patel, Yuan Zhuang, Mrigya Babuta, Jordi Gracia-Sancho and 1 more

Abstract read
In one paragraph

Article in JHEP reports : innovation in hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Martí Ortega-RiberaDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Radhika JoshiDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Sergi Guixé-MuntetLiver Vascular Biology Research Group, IDIBAPS Research Institute & CIBEREHD, Barcelona, Spain.
Veronika BrezaniDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Prashanth Thevkar NageshDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Viliam BrezaniDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Arman PatelDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Yuan ZhuangDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Mrigya BabutaDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jordi Gracia-SanchoLiver Vascular Biology Research Group, IDIBAPS Research Institute & CIBEREHD, Barcelona, Spain.
Gyongyi SzaboDepartment of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Funding

Alcohol and Monocyte Signaling Administrative SupplementR01AA011576 · NIAAA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Gyongyi Szabo · 1998 to 2026
$9.3M
TLR4 Signaling in alcoholic liver diseaseR01AA017729 · NIAAA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SZABO, GYONGYI · 2009 to 2021
$4.3M
Inflammasome activation in modulation of Alzheimer’s Disease by alcohol Administrative SupplementR01AG072899 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI GOLENBOCK, DOUGLAS T, SZABO, GYONGYI · 2020 to 2025
$2.4M
Innate immune dysregulation in alcohol-associated liver diseaseR01AA032418 · NIAAA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Gyongyi Szabo · 2025 to 2026
$1.4M
NIAAA NIH HHS R01 AA011576NIAAA NIH HHS R01 AA017729NIAAA NIH HHS R01 AA032418NIA NIH HHS R01 AG072899
6 · The paper itself

Abstract

Background & Aims: Aging and alcohol misuse independently alter monocyte (MO) and macrophage (MØ) function, leading to impaired antimicrobial responses. However, how alcohol misuse contributes to impaired MO/MØ function during aging remains unclear. Methods: We compared the transcriptomes of MOs and MØs from alcohol-modulated niches (liver, brain, and bone marrow [BM]) in young (3-month-old) and old (20-24-month-old) female C57BL/6N mice (n = 4-6 per group). Statistical significance was determined using two-way ANOVA. Results: MO/MØ transcriptomes showed unique organ-specific responses to aging and alcohol. Aging elicited a common deregulation of pathogen-responsive pathways, while alcohol misuse commonly inhibited IFN signaling in the aged populations. Our studies on intercellular communication using ligand-receptor interactions revealed that BM MOs were the least communicative and liver MØs were the most communicative. Alcohol misuse specifically increased MO/MØ communication in aging. We also identified and validated specific pathways driving inter-organ MO/MØ crosstalk in alcohol misuse during aging, including APOE-TREM2 signaling from the liver to microglia and the NRXN2 and SPP1 pathways. Conclusion: Our results provide a unique insight into the heterogeneity of the MO/MØ transcriptome and define the inter-organ crosstalk between BM, liver, and brain during aging and alcohol misuse. Impact and implications: Aging and alcohol misuse are linked to immune dysfunction, systemic inflammation, and altered innate immune responses. Here, we examined monocyte/macrophage responses in the liver, brain, and bone marrow of young and aged mice under alcohol exposure at the transcriptomic level. We observed that aging and alcohol predominantly elicited organ-specific changes in gene expression, with minimal overlap between the monocyte/macrophage populations across different tissues. However, aging commonly upregulated pathogen response pathways while alcohol misuse inhibited interferon signaling. We also assessed cell-cell communication by analyzing ligand-receptor expression in the different monocyte/macrophage populations and identified candidate molecules (APOE, TREM2, NRXN2, SPP1) from the top pathways guiding inter-organ signaling specifically in aging and alcohol misuse. Our findings have generated a unique repository and provide novel insights on how aging and alcohol impact tissue-specific monocytes/macrophages and their crosstalk.

Indexed as

communicationethanolinterferonmacrophagemicrogliamulti-organ

Identifiers

PMID41334456
PMCPMC12666552

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.