Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity

Shetty, Shishir; Lalor, Patricia F.; Adams, David H.

doi:10.1038/s41575-018-0020-y

Cited by 523Liver physiology and pathologyLiver Diseases and ImmunityLiver Disease and Transplantation

Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity

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Shetty, Shishir, Lalor, Patricia F., Adams, David H.·2018·Nature Reviews Gastroenterology & Hepatology

DOI 10.1038/s41575-018-0020-yPMC PMC7096836

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Abstract

Liver sinusoidal endothelial cells (LSECs) line the low shear, sinusoidal capillary channels of the liver and are the most abundant non-parenchymal hepatic cell population. LSECs do not simply form a barrier within the hepatic sinusoids but have vital physiological and immunological functions, including filtration, endocytosis, antigen presentation and leukocyte recruitment. Reflecting these multifunctional properties, LSECs display unique structural and phenotypic features that differentiate them from the capillary endothelium present within other organs. It is now clear that LSECs have a critical role in maintaining immune homeostasis within the liver and in mediating the immune response during acute and chronic liver injury. In this Review, we outline how LSECs influence the immune microenvironment within the liver and discuss their contribution to immune-mediated liver diseases and the complications of fibrosis and carcinogenesis.

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Sinusoidal endothelial cells in the liver experience mechanical stimulation from the bloodstream within the sinusoid, resulting in phenotypic alterations in HSCs and the release of ECM proteins.
“Sinusoidal endothelial cells in the liver experience mechanical stimulation from the bloodstream within the sinusoid, resulting in phenotypic alterations in HSCs and the release of ECM proteins.87”
From Mechanosensitive calcium ion channels Piezo1: A therapeutic target in liver disease (2025) · cites this paper as [87]
In “Interaction with other liver cells” (page unavailable), the review says LSECs maintain HSC quiescence, while LSEC capillarization permits HSC activation and fibrogenesis; it also identifies HSCs as producers of extracellular matrix in chronic liver disease. The review describes low shear stress in the sinusoids under “LSECs in inflammatory liver disease,” but does not link mechanical stimulation from blood flow to HSC changes or ECM production. (LLM, conf=0.86)
Experimental — accuracy not yet measured
LSECs express TLR4 receptors that recognise bacterial lipopolysaccharides and unique scavenger receptors such as CLEC4G that mediate endocytosis.
“Like KCs, LSECs express TLR4 receptors that recognise bacterial lipopolysaccharides and also express unique scavenger receptors such as CLEC4G that mediate endocytosis.139”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [139]

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Common Lymphatic Endothelial and Vascular Endothelial Receptor-1 Mediates the Transmigration of Regulatory T Cells across Human Hepatic Sinusoidal Endothelium
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Liver Myofibroblasts Regulate Infiltration and Positioning of Lymphocytes in Human Liver
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The Relationship between Fenestrations, Sieve Plates and Rafts in Liver Sinusoidal Endothelial Cells
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Unique Cell Type-Specific Junctional Complexes in Vascular Endothelium of Human and Rat Liver Sinusoids
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Human liver sinusoidal endothelial cells promote intracellular crawling of lymphocytes during recruitment- a new step in migration
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Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid
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Authors: Shetty, S., Lalor, P. F., & Adams, D. H.
Affiliations: University Hospitals Birmingham NHS Foundation Trust (GB)
Corresponding author: Adams, David H.
ORCID: Shetty, Shishir
Lalor, Patricia F.
Adams, David H.
Venue: Nature Reviews Gastroenterology & Hepatology
Publisher: Springer Science and Business Media LLC
Published: 2018-05-29
Volume: 15
Issue: 9
Pages: 555-567
ISSN: 1759-5045 (ISSN-L)
1759-5053
DOI: 10.1038/s41575-018-0020-y
PMC: PMC7096836
OpenAlex: W2807476445
Cited by: 523
References: 171
Citations by year: 2026: 71 · 2025: 74 · 2024: 103 · 2023: 58 · 2022: 81 · 2021: 65 · 2020: 50 · 2019: 18 · 2018: 3
FWCI: 4.62
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Gastroenterology & Hepatology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
Funders: University Hospitals Birmingham NHS Foundation Trust
National Institute for Health and Care Research
University of Birmingham
Birmingham Biomedical Research Centre
Topics: Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords: liver sinusoidal endothelial cells, hepatic immunity, immune homeostasis, immune-mediated liver disease, liver fibrosis, hepatocarcinogenesis, antigen presentation, leukocyte recruitment, endocytosis, immune microenvironment, liver injury
MeSH terms: Animals, Endothelium, Vascular, Humans, Immunity, Innate, Liver, Liver Diseases, Adaptive Immunity

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Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity

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