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Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells

T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1...

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Autores principales: Reinhold, Dirk, Guttek, Karina, Reddig, Annika, Voss, Linda, Schubert, Claudia, Kahlfuss, Sascha, Grüngreiff, Kurt, Schraven, Burkhart, Reinhold, Annegret
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998552/
https://www.ncbi.nlm.nih.gov/pubmed/33804583
http://dx.doi.org/10.3390/biomedicines9030246
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author Reinhold, Dirk
Guttek, Karina
Reddig, Annika
Voss, Linda
Schubert, Claudia
Kahlfuss, Sascha
Grüngreiff, Kurt
Schraven, Burkhart
Reinhold, Annegret
author_facet Reinhold, Dirk
Guttek, Karina
Reddig, Annika
Voss, Linda
Schubert, Claudia
Kahlfuss, Sascha
Grüngreiff, Kurt
Schraven, Burkhart
Reinhold, Annegret
author_sort Reinhold, Dirk
collection PubMed
description T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1/Th2/Th17 cytokine production of stimulated human and mouse T cells. To understand the suppressive effect of zinc on T cell function, we here investigated the influence of zinc aspartate on human T cells focusing on the secretion of immunosuppressive cytokines, induction of apoptosis, and caspase 3/7 activity. To this end, we monitored either freshly stimulated or pre-activated human T cells in the presence of zinc aspartate from 40–140 µM over a period of 72 h. Under both experimental conditions, we observed a dose-dependent suppression of human T cell proliferation. While IL-1ra, latent TGF-β1, and IL-10 were dose-dependently reduced, we, unexpectedly, detected elevated levels of IL-16 upon zinc supplementation. In addition, the number of cells with active caspase 3/7 and, consecutively, the amount of cells undergoing apoptosis, steadily increased at zinc aspartate concentrations exceeding 100 µM. Taken together, our findings suggest that zinc aspartate impairs T cell fitness and might be beneficial for the treatment of T cell-mediated autoimmune diseases.
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spelling pubmed-79985522021-03-28 Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells Reinhold, Dirk Guttek, Karina Reddig, Annika Voss, Linda Schubert, Claudia Kahlfuss, Sascha Grüngreiff, Kurt Schraven, Burkhart Reinhold, Annegret Biomedicines Article T cell activation mediates immunity to pathogens. On the flipside, T cells are also involved in pathological immune responses during chronic autoimmune diseases. We recently reported that zinc aspartate, a registered drug with high bioavailability, dose-dependently inhibits T cell activation and Th1/Th2/Th17 cytokine production of stimulated human and mouse T cells. To understand the suppressive effect of zinc on T cell function, we here investigated the influence of zinc aspartate on human T cells focusing on the secretion of immunosuppressive cytokines, induction of apoptosis, and caspase 3/7 activity. To this end, we monitored either freshly stimulated or pre-activated human T cells in the presence of zinc aspartate from 40–140 µM over a period of 72 h. Under both experimental conditions, we observed a dose-dependent suppression of human T cell proliferation. While IL-1ra, latent TGF-β1, and IL-10 were dose-dependently reduced, we, unexpectedly, detected elevated levels of IL-16 upon zinc supplementation. In addition, the number of cells with active caspase 3/7 and, consecutively, the amount of cells undergoing apoptosis, steadily increased at zinc aspartate concentrations exceeding 100 µM. Taken together, our findings suggest that zinc aspartate impairs T cell fitness and might be beneficial for the treatment of T cell-mediated autoimmune diseases. MDPI 2021-03-01 /pmc/articles/PMC7998552/ /pubmed/33804583 http://dx.doi.org/10.3390/biomedicines9030246 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Reinhold, Dirk
Guttek, Karina
Reddig, Annika
Voss, Linda
Schubert, Claudia
Kahlfuss, Sascha
Grüngreiff, Kurt
Schraven, Burkhart
Reinhold, Annegret
Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells
title Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells
title_full Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells
title_fullStr Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells
title_full_unstemmed Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells
title_short Zinc Aspartate Induces IL-16 Secretion and Apoptosis in Human T Cells
title_sort zinc aspartate induces il-16 secretion and apoptosis in human t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998552/
https://www.ncbi.nlm.nih.gov/pubmed/33804583
http://dx.doi.org/10.3390/biomedicines9030246
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