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25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent
INTRODUCTION: Human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) exhibit a tight bi-directional interaction with CD4(+) T lymphocytes. The hPDL-MSCs’ immunomodulatory abilities are drastically enhanced by pro-inflammatory cytokines via boosting the expression of various immunom...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902380/ https://www.ncbi.nlm.nih.gov/pubmed/36761739 http://dx.doi.org/10.3389/fimmu.2023.1100041 |
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author | Behm, Christian Blufstein, Alice Gahn, Johannes Moritz, Andreas Rausch-Fan, Xiaohui Andrukhov, Oleh |
author_facet | Behm, Christian Blufstein, Alice Gahn, Johannes Moritz, Andreas Rausch-Fan, Xiaohui Andrukhov, Oleh |
author_sort | Behm, Christian |
collection | PubMed |
description | INTRODUCTION: Human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) exhibit a tight bi-directional interaction with CD4(+) T lymphocytes. The hPDL-MSCs’ immunomodulatory abilities are drastically enhanced by pro-inflammatory cytokines via boosting the expression of various immunomediators. 25-hydroxyvitamin D(3) (25(OH)D(3)), the major metabolite of vitamin D3 in the blood, affects both hPDL-MSCs and CD4(+) T lymphocytes, but its influence on their interaction is unknown. METHODS: Therefore, primary hPDL-MSCs were stimulated in vitro with tumor necrosis factor (TNF)-α a or interleukin (IL)-1β in the absence and presence of 25(OH)D(3) followed by an indirect co-culture with phytohemagglutinin-activated CD4(+) T lymphocytes. The CD4(+) T lymphocyte proliferation, viability, and cytokine secretion were analyzed. Additionally, the expression of various immunomediators in hPDL-MSCs was investigated, and their implication was verified by using pharmacological inhibitors. RESULTS: 25(OH)D(3) significantly counteracted the suppressive effects of IL-1β-treated hPDL-MSCs on CD4(+) T lymphocyte proliferation, whereas no effects were observed in the presence of TNF-α. Additionally, 25(OH)D(3) significantly increased the percentage of viable CD4(+) T lymphocytes via TNF-α- or IL-1β-treated hPDL-MSCs. It also caused a significant decrease in interferon-γ, IL-17A, and transforming growth factor-β productions, which were triggered by TNF-α-treated hPDL-MSCs. 25(OH)D(3) significantly decreased the production of various immunomediators in hPDL-MSCs. Inhibition of two of them, prostaglandin E2 and indoleamine-2,3-dioxygenase-1, partially abolished some of the hPDL-MSCs-mediated effects of 25(OH)D(3) on CD4(+) T lymphocytes. CONCLUSION: These data indicate that 25(OH)D(3) influences the immunomodulatory activities of hPDL-MSCs. This modulatory potential seems to have high plasticity depending on the local cytokine conditions and may be involved in regulating periodontal tissue inflammatory processes. |
format | Online Article Text |
id | pubmed-9902380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99023802023-02-08 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent Behm, Christian Blufstein, Alice Gahn, Johannes Moritz, Andreas Rausch-Fan, Xiaohui Andrukhov, Oleh Front Immunol Immunology INTRODUCTION: Human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) exhibit a tight bi-directional interaction with CD4(+) T lymphocytes. The hPDL-MSCs’ immunomodulatory abilities are drastically enhanced by pro-inflammatory cytokines via boosting the expression of various immunomediators. 25-hydroxyvitamin D(3) (25(OH)D(3)), the major metabolite of vitamin D3 in the blood, affects both hPDL-MSCs and CD4(+) T lymphocytes, but its influence on their interaction is unknown. METHODS: Therefore, primary hPDL-MSCs were stimulated in vitro with tumor necrosis factor (TNF)-α a or interleukin (IL)-1β in the absence and presence of 25(OH)D(3) followed by an indirect co-culture with phytohemagglutinin-activated CD4(+) T lymphocytes. The CD4(+) T lymphocyte proliferation, viability, and cytokine secretion were analyzed. Additionally, the expression of various immunomediators in hPDL-MSCs was investigated, and their implication was verified by using pharmacological inhibitors. RESULTS: 25(OH)D(3) significantly counteracted the suppressive effects of IL-1β-treated hPDL-MSCs on CD4(+) T lymphocyte proliferation, whereas no effects were observed in the presence of TNF-α. Additionally, 25(OH)D(3) significantly increased the percentage of viable CD4(+) T lymphocytes via TNF-α- or IL-1β-treated hPDL-MSCs. It also caused a significant decrease in interferon-γ, IL-17A, and transforming growth factor-β productions, which were triggered by TNF-α-treated hPDL-MSCs. 25(OH)D(3) significantly decreased the production of various immunomediators in hPDL-MSCs. Inhibition of two of them, prostaglandin E2 and indoleamine-2,3-dioxygenase-1, partially abolished some of the hPDL-MSCs-mediated effects of 25(OH)D(3) on CD4(+) T lymphocytes. CONCLUSION: These data indicate that 25(OH)D(3) influences the immunomodulatory activities of hPDL-MSCs. This modulatory potential seems to have high plasticity depending on the local cytokine conditions and may be involved in regulating periodontal tissue inflammatory processes. Frontiers Media S.A. 2023-01-24 /pmc/articles/PMC9902380/ /pubmed/36761739 http://dx.doi.org/10.3389/fimmu.2023.1100041 Text en Copyright © 2023 Behm, Blufstein, Gahn, Moritz, Rausch-Fan and Andrukhov https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Behm, Christian Blufstein, Alice Gahn, Johannes Moritz, Andreas Rausch-Fan, Xiaohui Andrukhov, Oleh 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
title | 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
title_full | 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
title_fullStr | 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
title_full_unstemmed | 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
title_short | 25-hydroxyvitamin D(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
title_sort | 25-hydroxyvitamin d(3) generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902380/ https://www.ncbi.nlm.nih.gov/pubmed/36761739 http://dx.doi.org/10.3389/fimmu.2023.1100041 |
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