Review Article | Published:

Liver sinusoidal endothelial cells — gatekeepers of hepatic immunity

Nature Reviews Gastroenterology & Hepatology (2018) | Download Citation


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.

Key points

  • Liver sinusoidal endothelial cells (LSECs) that line the hepatic sinusoids have important physiological roles and mediate the filtration and scavenger functions of the liver.

  • LSECs also have innate and adaptive immunological functions, including antigen presentation and maintenance of the balance between tolerance and effector immune responses.

  • In inflammatory liver diseases, LSECs influence the composition of hepatic immune populations by mediating diapedesis of leukocyte subsets via distinct combinations of adhesion molecules and chemokines.

  • LSECs play a crucial part in the cellular crosstalk that regulates progressive chronic liver disease, which leads to fibrosis and carcinogenesis.

  • The role of LSECs in initiating immune responses and contributing to progressive liver disease makes them a potential therapeutic target for treating inflammatory liver diseases.

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The work of the authors is funded by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham National Health Service (NHS) Foundation Trust and the University of Birmingham. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the UK Department of Health.

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  1. Centre for Liver Research and NIHR Birmingham Biomedical Research Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

    • Shishir Shetty
    • , Patricia F. Lalor
    •  & David H. Adams
  2. Liver Unit, University Hospitals Birmingham NHS Trust, Birmingham, UK

    • Shishir Shetty
    • , Patricia F. Lalor
    •  & David H. Adams


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S.S. and P.F.L. researched data for the article, made substantial contributions to discussion of content and wrote the manuscript. D.H.A. reviewed and edited the manuscript before submission.

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The authors have no competing financial interests.

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Correspondence to David H. Adams.

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