Pleiotropic effects of vitamin D 3 on CD4 + T lymphocytes mediated by human periodontal ligament cells and inflammatory environment

Aims Both, vitamin D 3 and human periodontal ligament cells (hPDLCs) possess immunosuppressive properties, but their combined effect on immune cells has never been investigated. Here, we analysed the impact of vitamin D 3 on the immunosuppressive properties of hPDLCs towards CD4 + T lymphocytes. Material and Methods Allogenic CD4 + T lymphocytes were activated by phytohemagglutinin either in monoculture or co‐culture with hPDLCs, in the presence or absence of IFN‐γ and 1,25(OH) 2 D 3 . After 5 days, CD4 + T‐lymphocyte proliferation, CD4 + CD25 + FoxP3 + regulatory T lymphocytes (T regs ) proportion and IL‐10, TGF‐β1 and IL‐17A production were analysed. Results In monoculture, 1,25(OH) 2 D 3 suppressed CD4 + T‐lymphocyte proliferation, increased the percentage of CD4 + FoxP3 + CD25 + FoxP3 + T regs and enhanced IL‐10 and TGF‐β1 production. In the presence of IFN‐γ treated hPDLCs, 1,25(OH) 2 D 3 significantly increased CD4 + T‐lymphocyte proliferation and decreased the percentage of CD4 + CD25 + FoxP3 + T regs . IL‐10 and IL‐17A expression was significantly diminished by 1,25(OH) 2 D 3 , whereas TGF‐β1 was slightly increased. The effects of 1,25(OH) 2 D 3 in co‐culture were reversed by inhibition of indoleamine‐2,3‐dioxygenase‐1, prostaglandin‐endoperoxide synthase and programmed cell death 1 ligand 1. 1,25(OH) 2 D 3 also suppressed the expression of these proteins in hPDLCs. Conclusion Effects of vitamin D 3 on CD4 + T lymphocyte are modified by hPDLCs depending on the microenvironment.