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Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells
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 in...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853882/ https://www.ncbi.nlm.nih.gov/pubmed/31723203 http://dx.doi.org/10.1038/s41598-019-53234-x |
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author | Levring, Trine B. Kongsbak-Wismann, Martin Rode, Anna K. O. Al-Jaberi, Fatima A. H. Lopez, Daniel V. Met, Özcan Woetmann, Anders Bonefeld, Charlotte M. Ødum, Niels Geisler, Carsten |
author_facet | Levring, Trine B. Kongsbak-Wismann, Martin Rode, Anna K. O. Al-Jaberi, Fatima A. H. Lopez, Daniel V. Met, Özcan Woetmann, Anders Bonefeld, Charlotte M. Ødum, Niels Geisler, Carsten |
author_sort | Levring, Trine B. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6853882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68538822019-11-19 Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells Levring, Trine B. Kongsbak-Wismann, Martin Rode, Anna K. O. Al-Jaberi, Fatima A. H. Lopez, Daniel V. Met, Özcan Woetmann, Anders Bonefeld, Charlotte M. Ødum, Niels Geisler, Carsten Sci Rep Article 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. Nature Publishing Group UK 2019-11-13 /pmc/articles/PMC6853882/ /pubmed/31723203 http://dx.doi.org/10.1038/s41598-019-53234-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Levring, Trine B. Kongsbak-Wismann, Martin Rode, Anna K. O. Al-Jaberi, Fatima A. H. Lopez, Daniel V. Met, Özcan Woetmann, Anders Bonefeld, Charlotte M. Ødum, Niels Geisler, Carsten Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells |
title | Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells |
title_full | Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells |
title_fullStr | Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells |
title_full_unstemmed | Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells |
title_short | Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells |
title_sort | tumor necrosis factor induces rapid down-regulation of txnip in human t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853882/ https://www.ncbi.nlm.nih.gov/pubmed/31723203 http://dx.doi.org/10.1038/s41598-019-53234-x |
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