Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses

Abstract Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endot...

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Autores principales:	Hasitha Gunawardana, Tahmineh Romero, Ning Yao, Sebastiaan Heidt, Arend Mulder, David A. Elashoff, Nicole M. Valenzuela
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/947d20a2137c4e92853281b5f4120750
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spelling	oai:doaj.org-article:947d20a2137c4e92853281b5f41207502021-12-02T13:56:47ZTissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses10.1038/s41598-020-80102-w2045-2322https://doaj.org/article/947d20a2137c4e92853281b5f41207502021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80102-whttps://doaj.org/toc/2045-2322Abstract Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.Hasitha GunawardanaTahmineh RomeroNing YaoSebastiaan HeidtArend MulderDavid A. ElashoffNicole M. ValenzuelaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hasitha Gunawardana Tahmineh Romero Ning Yao Sebastiaan Heidt Arend Mulder David A. Elashoff Nicole M. Valenzuela Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
description	Abstract Endothelial cells (EC) coordinate vascular homeostasis and inflammation. In organ transplantation, EC are a direct alloimmune target. We posited that tissue specific heterogeneity of vascular EC may partly underlie the disparate organ-specific alloimmune risk. We examined the vascular endothelial response to inflammation across six primary endothelial beds from four major transplanted organs: the heart, lung, kidney and liver. First, we reanalyzed a public dataset of cardiac allograft rejection and found that endothelial inflammatory response genes were elevated in human cardiac allograft biopsies undergoing rejection compared with stable grafts. Next, the inducible inflammatory phenotypes of EC from heart, lung, kidney, and liver were characterized in vitro, focused on expression of adhesion molecules and chemokines, and recruitment of allogeneic peripheral blood mononuclear immune cells. Large vessel cardiac EC most highly upregulated VCAM-1, particularly compared with hepatic EC, supported greater leukocyte adhesion and had distinct chemokine profiles after stimulation with cytokines and complement. Differentially expressed gene candidates that are known regulators of cytokine signaling and inflammatory programming were verified in publicly available datasets of organ-specific endothelial transcriptomes. In summary, differential baseline expression of immune regulating genes may contribute to differential vascular inflammatory responses depending on organ.
format	article
author	Hasitha Gunawardana Tahmineh Romero Ning Yao Sebastiaan Heidt Arend Mulder David A. Elashoff Nicole M. Valenzuela
author_facet	Hasitha Gunawardana Tahmineh Romero Ning Yao Sebastiaan Heidt Arend Mulder David A. Elashoff Nicole M. Valenzuela
author_sort	Hasitha Gunawardana
title	Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
title_short	Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
title_full	Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
title_fullStr	Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
title_full_unstemmed	Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
title_sort	tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/947d20a2137c4e92853281b5f4120750
work_keys_str_mv	AT hasithagunawardana tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses AT tahminehromero tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses AT ningyao tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses AT sebastiaanheidt tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses AT arendmulder tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses AT davidaelashoff tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses AT nicolemvalenzuela tissuespecificendothelialcellheterogeneitycontributestounequalinflammatoryresponses
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Tissue-specific endothelial cell heterogeneity contributes to unequal inflammatory responses

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