ArticleJournal of leukocyte biology2013
Kupffer cells potentiate liver sinusoidal endothelial cell injury in sepsis by ligating programmed cell death ligand-1.
Article in Journal of leukocyte biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- Article
- Research Progress on the Immune Function of Liver Sinusoidal Endothelial Cells in Sepsis.Cells · 2025Review
- Vessel co-option: a unique vascular-immune niche in liver cancer.Frontiers in oncology · 2024Review
- Review
- Synthetically glycosylated antigens for the antigen-specific suppression of established immune responses.Nature biomedical engineering · 2023Article
- PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role.Journal of inflammation (London, England) · 2023Article
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
- Role of regulation of PD-1 and PD-L1 expression in sepsis.Frontiers in immunology · 2023Review
- The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways.Frontiers in immunology · 2023Review
- Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms.Science advances · 2022Article
- Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses.Journal for immunotherapy of cancer · 2022Article
- Dysregulation of immune checkpoint proteins in hepatocellular carcinoma: Impact on metabolic reprogramming.Current opinion in pharmacology · 2022Review
- [Expression and Role of PD-L1 in a Mouse Model of Necrotizing Enterocolitis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Article
- Mitogen-activated protein kinase phosphatase-1 controls PD-L1 expression by regulating type I interferon during systemic Escherichia coli infection.The Journal of biological chemistry · 2022Article
- Negative Immune Checkpoint Protein, VISTA, Regulates the CD4Frontiers in immunology · 2022Article
- The role of liver sinusoidal endothelial cells in cancer liver metastasis.American journal of cancer research · 2021Review
- Delicate Role of PD-L1/PD-1 Axis in Blood Vessel Inflammatory Diseases: Current Insight and Future Significance.International journal of molecular sciences · 2020Review
- Biomarkers and Associated Immune Mechanisms for Early Detection and Therapeutic Management of Sepsis.Immune network · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
PD-1 and PD-L1 have been reported to provide peripheral tolerance by inhibiting TCR-mediated activation. We have reported that PD-L1-/- animals are protected from sepsis-induced mortality and immune suppression. Whereas studies indicate that LSECs normally express PD-L1, which is also thought to maintain local immune liver tolerance by ligating the receptor PD-1 on T lymphocytes, the role of PD-L1 in the septic liver remains unknown. Thus, we hypothesized initially that PD-L1 expression on LSECs protects them from sepsis-induced injury. We noted that the increased vascular permeability and pSTAT3 protein expression in whole liver from septic animals were attenuated in the absence of PD-L1. Isolated LSECs taken from septic animals, which exhibited increased cell death, declining cell numbers, reduced cellular proliferation, and VEGFR2 expression (an angiogenesis marker), also showed improved cell numbers, proliferation, and percent VEGFR2(+) levels in the absence of PD-L1. We also observed that sepsis induced an increase of liver F4/80(+)PD-1(+)-expressing KCs and increased PD-L1 expression on LSECs. Interestingly, PD-L1 expression levels on LSECs decreased when PD-1(+)-expressing KCs were depleted with clodronate liposomes. Contrary to our original hypothesis, we document here that increased interactions between PD-1(+) KCs and PD-L1(+) LSECs appear to lead to the decline of normal endothelial function-essential to sustain vascular integrity and prevent ALF. Importantly, we uncover an underappreciated pathological aspect of PD-1:PD-L1 ligation during inflammation that is independent of its normal, immune-suppressive activity.
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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.