Cargando…
VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding
V-set and immunoglobulin domain-containing 4 (VSIG4) is a complement receptor of the immunoglobulin superfamily that is specifically expressed on tissue resident macrophages, and its many reported functions and binding partners suggest a complex role in immune function. VSIG4 is reported to have a r...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426322/ https://www.ncbi.nlm.nih.gov/pubmed/37341346 http://dx.doi.org/10.1093/glycob/cwad050 |
_version_ | 1785090032364683264 |
---|---|
author | Ebstein, Sarah Y Rafique, Ashique Zhou, Yi Krasco, Amanda Montalvo-Ortiz, Welby Yu, Lola Custodio, Luisaidy Adam, Rene C Bloch, Nicolin Lee, Ken Adewale, Funmilola Vergata, Dominic Luz, Antonio Coquery, Sebastien Daniel, Benjamin Ullman, Erica Franklin, Matthew C Hermann, Aynur Huang, Tammy Olson, William Davis, Samuel Murphy, Andrew J Sleeman, Matthew A Wei, Joyce Skokos, Dimitris |
author_facet | Ebstein, Sarah Y Rafique, Ashique Zhou, Yi Krasco, Amanda Montalvo-Ortiz, Welby Yu, Lola Custodio, Luisaidy Adam, Rene C Bloch, Nicolin Lee, Ken Adewale, Funmilola Vergata, Dominic Luz, Antonio Coquery, Sebastien Daniel, Benjamin Ullman, Erica Franklin, Matthew C Hermann, Aynur Huang, Tammy Olson, William Davis, Samuel Murphy, Andrew J Sleeman, Matthew A Wei, Joyce Skokos, Dimitris |
author_sort | Ebstein, Sarah Y |
collection | PubMed |
description | V-set and immunoglobulin domain-containing 4 (VSIG4) is a complement receptor of the immunoglobulin superfamily that is specifically expressed on tissue resident macrophages, and its many reported functions and binding partners suggest a complex role in immune function. VSIG4 is reported to have a role in immune surveillance as well as in modulating diverse disease phenotypes such as infections, autoimmune conditions, and cancer. However, the mechanism(s) governing VSIG4’s complex, context-dependent role in immune regulation remains elusive. Here, we identify cell surface and soluble glycosaminoglycans, specifically heparan sulfates, as novel binding partners of VSIG4. We demonstrate that genetic deletion of heparan sulfate synthesis enzymes or cleavage of cell-surface heparan sulfates reduced VSIG4 binding to the cell surface. Furthermore, binding studies demonstrate that VSIG4 interacts directly with heparan sulfates, with a preference for highly sulfated moieties and longer glycosaminoglycan chains. To assess the impact on VSIG4 biology, we show that heparan sulfates compete with known VSIG4 binding partners C3b and iC3b. Furthermore, mutagenesis studies indicate that this competition occurs through overlapping binding epitopes for heparan sulfates and complement on VSIG4. Together these data suggest a novel role for heparan sulfates in VSIG4-dependent immune modulation. |
format | Online Article Text |
id | pubmed-10426322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-104263222023-08-16 VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding Ebstein, Sarah Y Rafique, Ashique Zhou, Yi Krasco, Amanda Montalvo-Ortiz, Welby Yu, Lola Custodio, Luisaidy Adam, Rene C Bloch, Nicolin Lee, Ken Adewale, Funmilola Vergata, Dominic Luz, Antonio Coquery, Sebastien Daniel, Benjamin Ullman, Erica Franklin, Matthew C Hermann, Aynur Huang, Tammy Olson, William Davis, Samuel Murphy, Andrew J Sleeman, Matthew A Wei, Joyce Skokos, Dimitris Glycobiology Original Article V-set and immunoglobulin domain-containing 4 (VSIG4) is a complement receptor of the immunoglobulin superfamily that is specifically expressed on tissue resident macrophages, and its many reported functions and binding partners suggest a complex role in immune function. VSIG4 is reported to have a role in immune surveillance as well as in modulating diverse disease phenotypes such as infections, autoimmune conditions, and cancer. However, the mechanism(s) governing VSIG4’s complex, context-dependent role in immune regulation remains elusive. Here, we identify cell surface and soluble glycosaminoglycans, specifically heparan sulfates, as novel binding partners of VSIG4. We demonstrate that genetic deletion of heparan sulfate synthesis enzymes or cleavage of cell-surface heparan sulfates reduced VSIG4 binding to the cell surface. Furthermore, binding studies demonstrate that VSIG4 interacts directly with heparan sulfates, with a preference for highly sulfated moieties and longer glycosaminoglycan chains. To assess the impact on VSIG4 biology, we show that heparan sulfates compete with known VSIG4 binding partners C3b and iC3b. Furthermore, mutagenesis studies indicate that this competition occurs through overlapping binding epitopes for heparan sulfates and complement on VSIG4. Together these data suggest a novel role for heparan sulfates in VSIG4-dependent immune modulation. Oxford University Press 2023-06-21 /pmc/articles/PMC10426322/ /pubmed/37341346 http://dx.doi.org/10.1093/glycob/cwad050 Text en © The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Ebstein, Sarah Y Rafique, Ashique Zhou, Yi Krasco, Amanda Montalvo-Ortiz, Welby Yu, Lola Custodio, Luisaidy Adam, Rene C Bloch, Nicolin Lee, Ken Adewale, Funmilola Vergata, Dominic Luz, Antonio Coquery, Sebastien Daniel, Benjamin Ullman, Erica Franklin, Matthew C Hermann, Aynur Huang, Tammy Olson, William Davis, Samuel Murphy, Andrew J Sleeman, Matthew A Wei, Joyce Skokos, Dimitris VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding |
title | VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding |
title_full | VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding |
title_fullStr | VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding |
title_full_unstemmed | VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding |
title_short | VSIG4 interaction with heparan sulfates inhibits VSIG4–complement binding |
title_sort | vsig4 interaction with heparan sulfates inhibits vsig4–complement binding |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426322/ https://www.ncbi.nlm.nih.gov/pubmed/37341346 http://dx.doi.org/10.1093/glycob/cwad050 |
work_keys_str_mv | AT ebsteinsarahy vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT rafiqueashique vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT zhouyi vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT krascoamanda vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT montalvoortizwelby vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT yulola vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT custodioluisaidy vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT adamrenec vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT blochnicolin vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT leeken vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT adewalefunmilola vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT vergatadominic vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT luzantonio vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT coquerysebastien vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT danielbenjamin vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT ullmanerica vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT franklinmatthewc vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT hermannaynur vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT huangtammy vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT olsonwilliam vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT davissamuel vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT murphyandrewj vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT sleemanmatthewa vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT weijoyce vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding AT skokosdimitris vsig4interactionwithheparansulfatesinhibitsvsig4complementbinding |