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Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells

Earlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose...

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Autores principales: Prenek, Lilla, Litvai, Tímea, Balázs, Noémi, Kugyelka, Réka, Boldizsár, Ferenc, Najbauer, József, Németh, Péter, Berki, Timea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527366/
https://www.ncbi.nlm.nih.gov/pubmed/32737651
http://dx.doi.org/10.1007/s10495-020-01629-x
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author Prenek, Lilla
Litvai, Tímea
Balázs, Noémi
Kugyelka, Réka
Boldizsár, Ferenc
Najbauer, József
Németh, Péter
Berki, Timea
author_facet Prenek, Lilla
Litvai, Tímea
Balázs, Noémi
Kugyelka, Réka
Boldizsár, Ferenc
Najbauer, József
Németh, Péter
Berki, Timea
author_sort Prenek, Lilla
collection PubMed
description Earlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose (10(–6) M) in vitro dexamethasone (DX) treatment in mouse thymic- and splenic Tregs and CD4(+) T cells. Activation of both extrinsic and intrinsic apoptotic pathways started after 2 h of DX treatment in CD4 SP thymocytes and was 3 × higher than in CD4(+) splenocytes, while in Treg cells, weak activation of the extrinsic apoptotic pathway started only after 3 h. We also investigated the expression of 21 apoptosis-related molecules using a protein array and found higher level of both pro-and anti-apoptotic molecules in Tregs compared to CD4(+) T cells. 4 h in vitro DX treatment induced upregulation of most apoptosis-related molecules both in Tregs and CD4(+) T cells, except for the decrease of Bcl-2 expression in CD4(+) T cells. We found high basal cytosolic Ca(2+) levels in untreated Treg cells, which further increased after DX treatment, while the specific TCR-induced Ca(2+) signal was lower in Tregs than in CD4(+) T cells. Our results suggest that in the background of the relative apoptosis resistance of Treg cells to GCs might be their high basal cytosolic Ca(2+) level and upregulated Bcl-2 expression. In contrast, downregulation of Bcl-2 expression in CD4(+) T cells can explain their higher, DX-induced apoptosis sensitivity.
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spelling pubmed-75273662020-10-19 Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells Prenek, Lilla Litvai, Tímea Balázs, Noémi Kugyelka, Réka Boldizsár, Ferenc Najbauer, József Németh, Péter Berki, Timea Apoptosis Article Earlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose (10(–6) M) in vitro dexamethasone (DX) treatment in mouse thymic- and splenic Tregs and CD4(+) T cells. Activation of both extrinsic and intrinsic apoptotic pathways started after 2 h of DX treatment in CD4 SP thymocytes and was 3 × higher than in CD4(+) splenocytes, while in Treg cells, weak activation of the extrinsic apoptotic pathway started only after 3 h. We also investigated the expression of 21 apoptosis-related molecules using a protein array and found higher level of both pro-and anti-apoptotic molecules in Tregs compared to CD4(+) T cells. 4 h in vitro DX treatment induced upregulation of most apoptosis-related molecules both in Tregs and CD4(+) T cells, except for the decrease of Bcl-2 expression in CD4(+) T cells. We found high basal cytosolic Ca(2+) levels in untreated Treg cells, which further increased after DX treatment, while the specific TCR-induced Ca(2+) signal was lower in Tregs than in CD4(+) T cells. Our results suggest that in the background of the relative apoptosis resistance of Treg cells to GCs might be their high basal cytosolic Ca(2+) level and upregulated Bcl-2 expression. In contrast, downregulation of Bcl-2 expression in CD4(+) T cells can explain their higher, DX-induced apoptosis sensitivity. Springer US 2020-07-31 2020 /pmc/articles/PMC7527366/ /pubmed/32737651 http://dx.doi.org/10.1007/s10495-020-01629-x Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Prenek, Lilla
Litvai, Tímea
Balázs, Noémi
Kugyelka, Réka
Boldizsár, Ferenc
Najbauer, József
Németh, Péter
Berki, Timea
Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells
title Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells
title_full Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells
title_fullStr Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells
title_full_unstemmed Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells
title_short Regulatory T cells are less sensitive to glucocorticoid hormone induced apoptosis than CD4(+) T cells
title_sort regulatory t cells are less sensitive to glucocorticoid hormone induced apoptosis than cd4(+) t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527366/
https://www.ncbi.nlm.nih.gov/pubmed/32737651
http://dx.doi.org/10.1007/s10495-020-01629-x
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