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

Daniel A Patten; Sivesh K Kamarajah; Joanne M Rose; Joseph Tickle; Emma L Shepherd; David H Adams; Chris J Weston; Shishir Shetty

doi:10.1038/s41598-017-17928-4

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

Daniel A Patten
, Sivesh K Kamarajah
, Joanne M Rose
, Joseph Tickle
, Emma L Shepherd
, David H Adams
, Chris J Weston
, Shishir Shetty

University Hospitals Birmingham , Birmingham , UK.

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

13 Downloads (Pure)

Abstract

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.

Original language	English
Article number	17600
Number of pages	15
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-17928-4
Publication status	Published - 14 Dec 2017

Bibliographical note

© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0
( http://creativecommons.org/licenses/by/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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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

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10.1038/s41598-017-17928-4Licence: CC BY 4.0

s41598-017-17928-4
© 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 ( http://creativecommons.org/licenses/by/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.
Final published version, 6.9 MBLicence: CC BY 4.0

Cite this

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

abstract = "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.",

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",

author = "Patten, \{Daniel A\} and Kamarajah, \{Sivesh K\} and Rose, \{Joanne M\} and Joseph Tickle and Shepherd, \{Emma L\} and Adams, \{David H\} and Weston, \{Chris J\} and Shishir Shetty",

note = "{\textcopyright} 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 ( http://creativecommons.org/licenses/by/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.",

year = "2017",

month = dec,

day = "14",

doi = "10.1038/s41598-017-17928-4",

language = "English",

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T1 - SCARF-1 promotes adhesion of CD4+ T cells to human hepatic sinusoidal endothelium under conditions of shear stress

AU - Patten, Daniel A

AU - Kamarajah, Sivesh K

AU - Rose, Joanne M

AU - Tickle, Joseph

AU - Shepherd, Emma L

AU - Adams, David H

AU - Weston, Chris J

AU - Shetty, Shishir

N1 - © 2017 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 ( http://creativecommons.org/licenses/by/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.

PY - 2017/12/14

Y1 - 2017/12/14

N2 - 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.

AB - 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.

KW - CD4-Positive T-Lymphocytes/cytology

KW - Capillaries/cytology

KW - Cell Adhesion

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Liver/blood supply

KW - Liver Neoplasms/immunology

KW - Scavenger Receptors, Class F/metabolism

KW - Shear Strength

KW - Stress, Mechanical

UR - https://www.nature.com/articles/s41598-017-17928-4

U2 - 10.1038/s41598-017-17928-4

DO - 10.1038/s41598-017-17928-4

M3 - Article

C2 - 29242513

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 17600

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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