Competence Center Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
Clinical Division of Conservative Dentistry and Periodontology, University Clinic of Dentistry, Medical University of Vienna, Vienna, Austria.
Front Immunol. 2023 Jan 24;14:1100041. doi: 10.3389/fimmu.2023.1100041. eCollection 2023.
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 (25(OH)D), 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.
Therefore, primary hPDL-MSCs were stimulated with tumor necrosis factor (TNF)-α a or interleukin (IL)-1β in the absence and presence of 25(OH)D 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.
25(OH)D 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 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 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 on CD4 T lymphocytes.
These data indicate that 25(OH)D 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.
人牙周韧带间充质基质细胞（hPDL-MSCs）与 CD4 T 淋巴细胞之间存在紧密的双向相互作用。促炎细胞因子通过增强各种免疫调节剂的表达，极大地增强了 hPDL-MSCs 的免疫调节能力。25-羟维生素 D（25(OH)D）是血液中维生素 D3 的主要代谢产物，可影响 hPDL-MSCs 和 CD4 T 淋巴细胞，但它对两者相互作用的影响尚不清楚。
因此，我们用肿瘤坏死因子（TNF）-α或白细胞介素（IL）-1β刺激原代 hPDL-MSCs，在存在和不存在 25(OH)D 的情况下，随后与植物血凝素激活的 CD4 T 淋巴细胞进行间接共培养。分析 CD4 T 淋巴细胞的增殖、活力和细胞因子分泌。此外，我们还研究了 hPDL-MSCs 中各种免疫调节剂的表达，并通过使用药理学抑制剂验证了它们的作用。
25(OH)D 显著拮抗了 IL-1β处理的 hPDL-MSCs 对 CD4 T 淋巴细胞增殖的抑制作用，而 TNF-α处理时则无此作用。此外，25(OH)D 还通过 TNF-α或 IL-1β处理的 hPDL-MSCs 显著增加了 CD4 T 淋巴细胞的存活率。它还显著降低了由 TNF-α处理的 hPDL-MSCs 触发的干扰素-γ、IL-17A 和转化生长因子-β的产生。25(OH)D 显著降低了 hPDL-MSCs 中各种免疫调节剂的产生。抑制其中两种，前列腺素 E2 和吲哚胺 2,3-双加氧酶-1，部分消除了 25(OH)D 对 CD4 T 淋巴细胞的一些 hPDL-MSCs 介导的作用。
这些数据表明，25(OH)D 影响 hPDL-MSCs 的免疫调节活性。这种调节潜力似乎具有很高的可塑性，取决于局部细胞因子条件，并可能参与调节牙周组织炎症过程。
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