Endothelial CD34 expression and regulation of immune cell response in-vitro

Abstract Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis, inflammatory responses, control of transendothelial migration of circulating cells into the tissues, and formation of new blood vesse...

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Main Authors: Lousineh Arakelian, Julien Lion, Guillaume Churlaud, Rezlene Bargui, Briac Thierry, Evelyne Mutabazi, Patrick Bruneval, Antonio José Alberdi, Christelle Doliger, Maëva Veyssiere, Jérôme Larghero, Nuala Mooney
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-40622-7
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author Lousineh Arakelian
Julien Lion
Guillaume Churlaud
Rezlene Bargui
Briac Thierry
Evelyne Mutabazi
Patrick Bruneval
Antonio José Alberdi
Christelle Doliger
Maëva Veyssiere
Jérôme Larghero
Nuala Mooney
author_facet Lousineh Arakelian
Julien Lion
Guillaume Churlaud
Rezlene Bargui
Briac Thierry
Evelyne Mutabazi
Patrick Bruneval
Antonio José Alberdi
Christelle Doliger
Maëva Veyssiere
Jérôme Larghero
Nuala Mooney
author_sort Lousineh Arakelian
collection DOAJ
description Abstract Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis, inflammatory responses, control of transendothelial migration of circulating cells into the tissues, and formation of new blood vessels. Therefore, understanding these cells is of major interest. The morphological features, phenotype and function of endothelial cells varies according to the vascular bed examined. The sialomucin, CD34, is widely used as an endothelial marker. However, CD34 is differentially expressed on endothelial cells in different organs and in pathological conditions. Little is known about regulation of endothelial CD34 expression or function. Expression of CD34 is also strongly regulated in-vitro in endothelial cell models, including human umbilical vein endothelial cells (HUVEC) and endothelial colony forming cells (ECFC). We have therefore analysed the expression and function of CD34 by comparing CD34high and CD34low endothelial cell subpopulations. Transcriptomic analysis showed that CD34 gene and protein expressions are highly correlated, that CD34high cells proliferate less but express higher levels of IL-33 and Angiopoietin 2, compared with CD34low cells. Higher secretion levels of IL-33 and Angiopoietin 2 by CD34high HUVECs was confirmed by ELISA. Finally, when endothelial cells were allowed to interact with peripheral blood mononuclear cells, CD34high endothelial cells activated stronger proliferation of regulatory T lymphocytes (Tregs) compared to CD34low cells whereas expansion of other CD4+-T cell subsets was equivalent. These results suggest that CD34 expression by endothelial cells in-vitro associates with their ability to proliferate and with an immunogenic ability that favours the tolerogenic response.
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spelling doaj.art-11f59db2b88d47ed9bfb389da8db60932023-11-26T12:58:24ZengNature PortfolioScientific Reports2045-23222023-08-0113111210.1038/s41598-023-40622-7Endothelial CD34 expression and regulation of immune cell response in-vitroLousineh Arakelian0Julien Lion1Guillaume Churlaud2Rezlene Bargui3Briac Thierry4Evelyne Mutabazi5Patrick Bruneval6Antonio José Alberdi7Christelle Doliger8Maëva Veyssiere9Jérôme Larghero10Nuala Mooney11Human Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Human Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976AP-HP, Hôpital Saint-Louis, Centre MEARY de Thérapie Cellulaire et GéniqueHuman Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Human Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Human Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Service de Cardiologie, Hôpital Européen Georges PompidouUMS Saint-Louis US53/UAR2030, Université Paris Cité - INSERM – CNRS, Institut de Recherche Saint LouisUMS Saint-Louis US53/UAR2030, Université Paris Cité - INSERM – CNRS, Institut de Recherche Saint LouisHuman Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Human Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Human Immunology, Pathophysiology, Immunotherapy, Inserm UMR 976Abstract Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis, inflammatory responses, control of transendothelial migration of circulating cells into the tissues, and formation of new blood vessels. Therefore, understanding these cells is of major interest. The morphological features, phenotype and function of endothelial cells varies according to the vascular bed examined. The sialomucin, CD34, is widely used as an endothelial marker. However, CD34 is differentially expressed on endothelial cells in different organs and in pathological conditions. Little is known about regulation of endothelial CD34 expression or function. Expression of CD34 is also strongly regulated in-vitro in endothelial cell models, including human umbilical vein endothelial cells (HUVEC) and endothelial colony forming cells (ECFC). We have therefore analysed the expression and function of CD34 by comparing CD34high and CD34low endothelial cell subpopulations. Transcriptomic analysis showed that CD34 gene and protein expressions are highly correlated, that CD34high cells proliferate less but express higher levels of IL-33 and Angiopoietin 2, compared with CD34low cells. Higher secretion levels of IL-33 and Angiopoietin 2 by CD34high HUVECs was confirmed by ELISA. Finally, when endothelial cells were allowed to interact with peripheral blood mononuclear cells, CD34high endothelial cells activated stronger proliferation of regulatory T lymphocytes (Tregs) compared to CD34low cells whereas expansion of other CD4+-T cell subsets was equivalent. These results suggest that CD34 expression by endothelial cells in-vitro associates with their ability to proliferate and with an immunogenic ability that favours the tolerogenic response.https://doi.org/10.1038/s41598-023-40622-7
spellingShingle Lousineh Arakelian
Julien Lion
Guillaume Churlaud
Rezlene Bargui
Briac Thierry
Evelyne Mutabazi
Patrick Bruneval
Antonio José Alberdi
Christelle Doliger
Maëva Veyssiere
Jérôme Larghero
Nuala Mooney
Endothelial CD34 expression and regulation of immune cell response in-vitro
Scientific Reports
title Endothelial CD34 expression and regulation of immune cell response in-vitro
title_full Endothelial CD34 expression and regulation of immune cell response in-vitro
title_fullStr Endothelial CD34 expression and regulation of immune cell response in-vitro
title_full_unstemmed Endothelial CD34 expression and regulation of immune cell response in-vitro
title_short Endothelial CD34 expression and regulation of immune cell response in-vitro
title_sort endothelial cd34 expression and regulation of immune cell response in vitro
url https://doi.org/10.1038/s41598-023-40622-7
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