Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

Trine B. Levring; Martin Kongsbak-Wismann; Anna K.O. Rode; Fatima A.H. Al-Jaberi; Daniel V. Lopez; Özcan Met; Anders Woetmann; Charlotte M. Bonefeld; Niels Ødum; Carsten Geisler

doi:10.1038/s41598-019-53234-x

Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

Trine B. Levring, Martin Kongsbak-Wismann, Anna K.O. Rode, Fatima A.H. Al-Jaberi, Daniel V. Lopez, Özcan Met, Anders Woetmann, Charlotte M. Bonefeld, Niels Ødum, Carsten Geisler^*

^*Corresponding author af dette arbejde

4 Citationer (Scopus)

4 Downloads (Pure)

Abstract

In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

Originalsprog	Engelsk
Artikelnummer	16725
Tidsskrift	Scientific Reports
Vol/bind	9
Antal sider	13
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-019-53234-x
Status	Udgivet - 2019

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10.1038/s41598-019-53234-xLicens: CC BY

Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cellsForlagets udgivne version, 1,86 MBLicens: CC BY

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title = "Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells",

abstract = "In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that na{\"i}ve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.",

author = "Levring, {Trine B.} and Martin Kongsbak-Wismann and Rode, {Anna K.O.} and Al-Jaberi, {Fatima A.H.} and Lopez, {Daniel V.} and {\"O}zcan Met and Anders Woetmann and Bonefeld, {Charlotte M.} and Niels {\O}dum and Carsten Geisler",

year = "2019",

doi = "10.1038/s41598-019-53234-x",

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journal = "Scientific Reports",

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T1 - Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

AU - Levring, Trine B.

AU - Kongsbak-Wismann, Martin

AU - Rode, Anna K.O.

AU - Al-Jaberi, Fatima A.H.

AU - Lopez, Daniel V.

AU - Met, Özcan

AU - Woetmann, Anders

AU - Bonefeld, Charlotte M.

AU - Ødum, Niels

AU - Geisler, Carsten

PY - 2019

Y1 - 2019

N2 - In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

AB - In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.

U2 - 10.1038/s41598-019-53234-x

DO - 10.1038/s41598-019-53234-x

M3 - Journal article

C2 - 31723203

AN - SCOPUS:85074959264

SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 16725

ER -

Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells

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