ArticleCellular and molecular gastroenterology and hepatology2025
Congestion Enriches Intra-hepatic Macrophages Through Reverse Zonation of CXCL9 in Liver Sinusoidal Endothelial Cells.
Article in Cellular and molecular gastroenterology and hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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.
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.
Who cites it
7 citing papers in PubMed.
- Production system-associated hepatic histomorphometric adaptations in swine: Comparative analysis of glycogen deposition, Kupffer cell abundance, and liver microarchitecture.Veterinary world · 2026Article
- Haemodynamic control of zonated liver function via instructive vascular Wnt signalling.Nature communications · 2026Article
- Liver sinusoidal endothelial cell fenestrations in metabolic liver disease: from molecular mechanisms to therapeutic perspectives.Cell communication and signaling : CCS · 2026Review
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Identification of CTSK as a TLR-related critical biomarker in liver cirrhosis via integrative bioinformatics and pathological characterization.Scientific reports · 2025Article
- Fontan-Associated Liver Disease.Seminars in liver disease · 2025Review
- Liver Traffic Jam: How Sinusoidal Congestion Rewires Macrophage Distribution via CXCL9.Cellular and molecular gastroenterology and hepatology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
BACKGROUND &
aimsCongestion alters the microenvironment of the liver sinusoid along the portal-central axis. We studied spatial changes in immune cells in the sinusoid that contribute to congestive fibrosis and portal hypertension (PHTN).
methodsTo visualize the distribution of immune cells in congestive hepatopathy (CH), we performed imaging mass cytometry (IMC) on liver tissue from patients with CH, Fontan-associated liver disease (FALD), and controls. We performed partial ligation of the inferior vena cava (pIVCL) to simulate CH in mice and isolated primary liver cells for single-cell RNA-sequencing (scRNA-seq) to study zonation of liver sinusoidal endothelial cells (LSECs). After pIVCL, mice were treated with intraperitoneal injections of AMG487, an inhibitor of the CXCL9 receptor, or a neutralizing antibody to CXCL9.
resultsIntra-hepatic macrophages are enriched in CH and FALD. Given the role of CXCL9 in macrophage patterning in the liver, we performed RNA in situ hybridization (RNAish) in CH and determined that CXCL9 was highly expressed in LSECs in FALD, suggesting that LSECs recruit macrophages in CH. After pIVCL, treatment with AMG487 or an antibody to CXCL9 attenuated portal pressures, fibrosis, and intra-hepatic macrophages. To study changes in LSECs that promote macrophage chemotaxis, we performed scRNA-seq after pIVCL and sham procedures. Analysis revealed 3 LSEC subpopulations according to sinusoidal location. RNAish identified peri-central LSECs as the predominant source of CXCL9 in FALD. In vitro analyses revealed that β-catenin and hypoxia inducible factor-1 α regulate CXCL9 transcription in peri-central LSECs.
conclusionsCXCL9 derived from peri-central LSECs enriches intra-hepatic macrophages in CH and FALD, contributing to congestive fibrosis and PHTN. Strategies to target LSEC-derived CXCL9 may prevent the progression of CH and FALD.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.