SCARF-1 promotes adhesion of CD4+ T cells to human hepatic sinusoidal endothelium under conditions of shear stress


Liver-resident cells are constantly exposed to gut-derived antigens via portal blood and, as a consequence, they express a unique repertoire of scavenger receptors. Whilst there is increasing evidence that the gut contributes to chronic inflammatory liver disease, the role of scavenger receptors in regulating liver inflammation remains limited. Here, we describe for the first time the expression of scavenger receptor class F, member 1 (SCARF-1) on hepatic sinusoidal endothelial cells (HSEC). We report that SCARF-1 shows a highly localised expression pattern and co-localised with endothelial markers on sinusoidal endothelium. Analysis of chronically inflamed liver tissue demonstrated accumulation of SCARF-1 at sites of CD4+ T cell aggregation. We then studied the regulation and functional role of SCARF-1 in HSEC and showed that SCARF-1 expression by HSEC is regulated by proinflammatory cytokines and bacterial lipopolysaccharide (LPS). Furthermore, SCARF-1 expression by HSEC, induced by proinflammatory and gut-derived factors acts as a novel adhesion molecule, present in adhesive cup structures, that specifically supports CD4+ T cells under conditions of physiological shear stress. In conclusion, we show that SCARF-1 contributes to lymphocyte subset adhesion to primary human HSEC and could play an important role in regulating the inflammatory response during chronic liver disease.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
Additional Information: © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 ( International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Uncontrolled Keywords: CD4-Positive T-Lymphocytes/cytology,Capillaries/cytology,Cell Adhesion,Gene Expression Regulation, Neoplastic,Humans,Liver/blood supply,Liver Neoplasms/immunology,Scavenger Receptors, Class F/metabolism,Shear Strength,Stress, Mechanical
Publication ISSN: 2045-2322
Last Modified: 10 Apr 2024 07:25
Date Deposited: 04 Nov 2022 12:31
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Related URLs: https://www.nat ... 598-017-17928-4 (Publisher URL)
PURE Output Type: Article
Published Date: 2017-12-14
Accepted Date: 2017-11-30
Authors: Patten, Daniel A
Kamarajah, Sivesh K
Rose, Joanne M
Tickle, Joseph
Shepherd, Emma L (ORCID Profile 0000-0002-1345-1746)
Adams, David H
Weston, Chris J
Shetty, Shishir



Version: Published Version

License: Creative Commons Attribution

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