25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent
IntroductionHuman 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 immunomedia...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100041/full |
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| author | Christian Behm Alice Blufstein Alice Blufstein Johannes Gahn Andreas Moritz Xiaohui Rausch-Fan Xiaohui Rausch-Fan Oleh Andrukhov |
| author_facet | Christian Behm Alice Blufstein Alice Blufstein Johannes Gahn Andreas Moritz Xiaohui Rausch-Fan Xiaohui Rausch-Fan Oleh Andrukhov |
| author_sort | Christian Behm |
| collection | DOAJ |
| description | IntroductionHuman 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 D3 (25(OH)D3), 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.MethodsTherefore, 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)D3 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.Results25(OH)D3 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)D3 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)D3 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)D3 on CD4+ T lymphocytes.ConclusionThese data indicate that 25(OH)D3 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. |
| first_indexed | 2024-04-10T20:48:10Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T20:48:10Z |
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| spelling | doaj.art-91097389b2f24f28a83e8fb045f1cac42023-01-24T05:11:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.1100041110004125-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependentChristian Behm0Alice Blufstein1Alice Blufstein2Johannes Gahn3Andreas Moritz4Xiaohui Rausch-Fan5Xiaohui Rausch-Fan6Oleh Andrukhov7Competence Center Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaCompetence Center Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaClinical Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaCompetence Center Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaClinical Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaClinical Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaCenter for Clinical Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaCompetence Center Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, AustriaIntroductionHuman 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 D3 (25(OH)D3), 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.MethodsTherefore, 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)D3 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.Results25(OH)D3 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)D3 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)D3 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)D3 on CD4+ T lymphocytes.ConclusionThese data indicate that 25(OH)D3 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100041/full25-hydroxyvitamin D3mesenchymal stromal cellsperiodontal ligamentimmunomodulationtumor necrosis factor alphainterleukin-1 beta |
| spellingShingle | Christian Behm Alice Blufstein Alice Blufstein Johannes Gahn Andreas Moritz Xiaohui Rausch-Fan Xiaohui Rausch-Fan Oleh Andrukhov 25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent Frontiers in Immunology 25-hydroxyvitamin D3 mesenchymal stromal cells periodontal ligament immunomodulation tumor necrosis factor alpha interleukin-1 beta |
| title | 25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
| title_full | 25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
| title_fullStr | 25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
| title_full_unstemmed | 25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
| title_short | 25-hydroxyvitamin D3 generates immunomodulatory plasticity in human periodontal ligament-derived mesenchymal stromal cells that is inflammatory context-dependent |
| title_sort | 25 hydroxyvitamin d3 generates immunomodulatory plasticity in human periodontal ligament derived mesenchymal stromal cells that is inflammatory context dependent |
| topic | 25-hydroxyvitamin D3 mesenchymal stromal cells periodontal ligament immunomodulation tumor necrosis factor alpha interleukin-1 beta |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100041/full |
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