Abstract
Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)2D3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)2D3 on the proliferation of allogenic CD4+ T lymphocyte or on the functional status of primary CD68+ macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)2D3 on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)2D3 increased or decreased CD4+ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)2D3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)2D3 significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)2D3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.
Highlights
Vitamin D3 is a hormone involved in controlling bone and calcium homeostasis [1] and in regulating immune response [2]
We investigated the effects of vitamin D3 in the presence of either tumor necrosis factor (TNF)-α, IL-1β, or IFN-γ, because these cytokines activate different signaling pathways, and different immunomodulatory aspects
The results indicate that 1,25(OH)2D3 modulates the immunomodulatory activities of hPDLSCs against CD4+ T lymphocytes and CD68+ macrophages differently, depending on the inflammatory cytokine context
Summary
Vitamin D3 is a hormone involved in controlling bone and calcium homeostasis [1] and in regulating immune response [2]. HPDLSCs are a heterogeneous cell population, showing a fibroblast-like morphology [10] They are multipotent and non-hematopoietic progenitor cells having a self-renewal potential [11]. Local inflammatory processes trigger hPDLSC migration to injured and inflamed periodontal tissue, mainly through chemotaxis. There, they are involved in controlling periodontal tissue regeneration and homeostasis, mainly by influencing local immune responses [15,16,17]
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