CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression

T cells and endothelial cells engage in bidirectional communication that regulates angiogenesis and T cell transmigration. Extracellular vesicles (EVs) mediate intercellular communication by the transfer of bioactive molecules including RNAs. EVs produced by a given cell type are heterogeneous in th...

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Autores principales: Sukhbir Kaur, Abdel G. Elkahloun, Jennifer D. Petersen, Anush Arakelyan, Ferenc Livak, Satya P. Singh, Leonid Margolis, Joshua Zimmerberg, David D. Roberts
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:65dcaa0b024640f7ab18112353ea5d402021-11-25T16:51:00ZCD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression10.3390/biomedicines91117052227-9059https://doaj.org/article/65dcaa0b024640f7ab18112353ea5d402021-11-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1705https://doaj.org/toc/2227-9059T cells and endothelial cells engage in bidirectional communication that regulates angiogenesis and T cell transmigration. Extracellular vesicles (EVs) mediate intercellular communication by the transfer of bioactive molecules including RNAs. EVs produced by a given cell type are heterogeneous in their RNA content, but it is unclear how specific EV surface markers relate to their functional effects on target cells. Our previous work established that Jurkat T cell EVs bearing CD63, MHC-I, or CD47 surface markers contain distinct noncoding RNA populations. The present study reveals that CD63<sup>+</sup> and MHC-I<sup>+</sup> EVs from CD47-deficient Jurkat T cells are enriched in small non-coding RNAs relative to EVs from wild-type Jurkat T cells. CD47-deficient Jurkat T cells secrete more CD63<sup>+</sup> and MHC-I<sup>+</sup> EVs, but MHC-I<sup>+</sup> EVs are selectively taken up more by human umbilical vein endothelial cells. Transcriptomics analysis of endothelial cells treated with CD63<sup>+</sup> or MHC-I<sup>+</sup> EVs showed surface marker- and CD47-dependent changes in gene expression in the target cells. Gene set enrichment analysis identified CD47-dependent, and surface marker-dependent effects of T cell EVs on VEGF and inflammatory signaling, cell cycle, and lipid and cholesterol metabolism. Thus, subsets of T cell EVs differentially regulate endothelial cell metabolism and inflammatory and angiogenic responses.Sukhbir KaurAbdel G. ElkahlounJennifer D. PetersenAnush ArakelyanFerenc LivakSatya P. SinghLeonid MargolisJoshua ZimmerbergDavid D. RobertsMDPI AGarticleextracellular vesiclesnon-coding RNAscell-cell communicationBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1705, p 1705 (2021)
institution DOAJ
collection DOAJ
language EN
topic extracellular vesicles
non-coding RNAs
cell-cell communication
Biology (General)
QH301-705.5
spellingShingle extracellular vesicles
non-coding RNAs
cell-cell communication
Biology (General)
QH301-705.5
Sukhbir Kaur
Abdel G. Elkahloun
Jennifer D. Petersen
Anush Arakelyan
Ferenc Livak
Satya P. Singh
Leonid Margolis
Joshua Zimmerberg
David D. Roberts
CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression
description T cells and endothelial cells engage in bidirectional communication that regulates angiogenesis and T cell transmigration. Extracellular vesicles (EVs) mediate intercellular communication by the transfer of bioactive molecules including RNAs. EVs produced by a given cell type are heterogeneous in their RNA content, but it is unclear how specific EV surface markers relate to their functional effects on target cells. Our previous work established that Jurkat T cell EVs bearing CD63, MHC-I, or CD47 surface markers contain distinct noncoding RNA populations. The present study reveals that CD63<sup>+</sup> and MHC-I<sup>+</sup> EVs from CD47-deficient Jurkat T cells are enriched in small non-coding RNAs relative to EVs from wild-type Jurkat T cells. CD47-deficient Jurkat T cells secrete more CD63<sup>+</sup> and MHC-I<sup>+</sup> EVs, but MHC-I<sup>+</sup> EVs are selectively taken up more by human umbilical vein endothelial cells. Transcriptomics analysis of endothelial cells treated with CD63<sup>+</sup> or MHC-I<sup>+</sup> EVs showed surface marker- and CD47-dependent changes in gene expression in the target cells. Gene set enrichment analysis identified CD47-dependent, and surface marker-dependent effects of T cell EVs on VEGF and inflammatory signaling, cell cycle, and lipid and cholesterol metabolism. Thus, subsets of T cell EVs differentially regulate endothelial cell metabolism and inflammatory and angiogenic responses.
format article
author Sukhbir Kaur
Abdel G. Elkahloun
Jennifer D. Petersen
Anush Arakelyan
Ferenc Livak
Satya P. Singh
Leonid Margolis
Joshua Zimmerberg
David D. Roberts
author_facet Sukhbir Kaur
Abdel G. Elkahloun
Jennifer D. Petersen
Anush Arakelyan
Ferenc Livak
Satya P. Singh
Leonid Margolis
Joshua Zimmerberg
David D. Roberts
author_sort Sukhbir Kaur
title CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression
title_short CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression
title_full CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression
title_fullStr CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression
title_full_unstemmed CD63<sup>+</sup> and MHC Class I<sup>+</sup> Subsets of Extracellular Vesicles Produced by Wild-Type and CD47-Deficient Jurkat T Cells Have Divergent Functional Effects on Endothelial Cell Gene Expression
title_sort cd63<sup>+</sup> and mhc class i<sup>+</sup> subsets of extracellular vesicles produced by wild-type and cd47-deficient jurkat t cells have divergent functional effects on endothelial cell gene expression
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/65dcaa0b024640f7ab18112353ea5d40
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