Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)

Abstract Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how...

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Autores principales:	Hee Young Kim, Tae-Hyun Yoo, Yuri Hwang, Ga Hye Lee, Bonah Kim, Jiyeon Jang, Hee Tae Yu, Min Chang Kim, Joo-Youn Cho, Chan Joo Lee, Hyeon Chang Kim, Sungha Park, Won-Woo Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36d7036dc04c4c71b5c849be06466d4b
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spelling	oai:doaj.org-article:36d7036dc04c4c71b5c849be06466d4b2021-12-02T12:32:14ZIndoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)10.1038/s41598-017-03130-z2045-2322https://doaj.org/article/36d7036dc04c4c71b5c849be06466d4b2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03130-zhttps://doaj.org/toc/2045-2322Abstract Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how uremic toxins affect cellular immunity and the mechanisms underlying pathogenesis of atherosclerosis in ESRD patients. Here, we investigated the characteristics of monocytes and CD4+ T cells in ESRD patients and the immune responses induced by indoxyl sulfate (IS), a key uremic toxin, in order to explore the pathogenic effects of these cells on vascular endothelial cells. In ESRD patients, monocytes respond to IS through the aryl hydrocarbon receptor (AhR) and consequently produce increased levels of TNF-α. Upon stimulation with TNF-α, human vascular endothelial cells produce copious amounts of CX3CL1, a chemokine ligand of CX3CR1 that is highly expressed on CD4+CD28−T cells, the predominantly expanded cell type in ESRD patients. A migration assay showed that CD4+CD28− T cells were preferentially recruited by CX3CL1. Moreover, activated CD4+CD28− T cells exhibited cytotoxic capability allowing for the induction of apoptosis in HUVECs. Our findings suggest that in ESRD, IS-mediated immune dysfunction may cause vascular endothelial cell damage and thus, this toxin plays a pivotal role in the pathogenesis of CVD.Hee Young KimTae-Hyun YooYuri HwangGa Hye LeeBonah KimJiyeon JangHee Tae YuMin Chang KimJoo-Youn ChoChan Joo LeeHyeon Chang KimSungha ParkWon-Woo LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hee Young Kim Tae-Hyun Yoo Yuri Hwang Ga Hye Lee Bonah Kim Jiyeon Jang Hee Tae Yu Min Chang Kim Joo-Youn Cho Chan Joo Lee Hyeon Chang Kim Sungha Park Won-Woo Lee Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
description	Abstract Progressive renal failure causes uremia-related immune dysfunction, which features a chronic inflammatory milieu. Given the central role of end-stage renal disease (ESRD)-related immune dysfunction in the pathogenesis of cardiovascular diseases (CVDs), much attention has been focused on how uremic toxins affect cellular immunity and the mechanisms underlying pathogenesis of atherosclerosis in ESRD patients. Here, we investigated the characteristics of monocytes and CD4+ T cells in ESRD patients and the immune responses induced by indoxyl sulfate (IS), a key uremic toxin, in order to explore the pathogenic effects of these cells on vascular endothelial cells. In ESRD patients, monocytes respond to IS through the aryl hydrocarbon receptor (AhR) and consequently produce increased levels of TNF-α. Upon stimulation with TNF-α, human vascular endothelial cells produce copious amounts of CX3CL1, a chemokine ligand of CX3CR1 that is highly expressed on CD4+CD28−T cells, the predominantly expanded cell type in ESRD patients. A migration assay showed that CD4+CD28− T cells were preferentially recruited by CX3CL1. Moreover, activated CD4+CD28− T cells exhibited cytotoxic capability allowing for the induction of apoptosis in HUVECs. Our findings suggest that in ESRD, IS-mediated immune dysfunction may cause vascular endothelial cell damage and thus, this toxin plays a pivotal role in the pathogenesis of CVD.
format	article
author	Hee Young Kim Tae-Hyun Yoo Yuri Hwang Ga Hye Lee Bonah Kim Jiyeon Jang Hee Tae Yu Min Chang Kim Joo-Youn Cho Chan Joo Lee Hyeon Chang Kim Sungha Park Won-Woo Lee
author_facet	Hee Young Kim Tae-Hyun Yoo Yuri Hwang Ga Hye Lee Bonah Kim Jiyeon Jang Hee Tae Yu Min Chang Kim Joo-Youn Cho Chan Joo Lee Hyeon Chang Kim Sungha Park Won-Woo Lee
author_sort	Hee Young Kim
title	Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
title_short	Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
title_full	Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
title_fullStr	Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
title_full_unstemmed	Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)
title_sort	indoxyl sulfate (is)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (esrd)
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/36d7036dc04c4c71b5c849be06466d4b
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Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD)

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