Activation of TLR3 Enhance Stemness and Immunomodulatory Properties of Periodontal Ligament Stem Cells (PDLSCs)

Periodontal ligament stem cells (PDLSCs) have been served as a cell reservoir for tissue regeneration during adulthood. For clinical applications, the challenging steps are to maintain the stem cell properties and to improve the regeneration capacity of PDLSCs during culture. Toll-like receptor 3 (TLR3) signaling has been shown to enhance therapeutic potential in several cell types including mesenchymal stem cells (MSCs) by inducing the secretion of multifunctional trophic factors. However, the role of TLR3 in PDLSCs is still unknown. The aim of this study was to investigate the responses of PDLSCs after TLR3 engagement using TLR3 agonist, poly(I:C). The result indicated that stimulation of TLR3 significantly enhanced pluripotent stem cell gene expression (e.g., REX-1 and SOX2) as well as immunomodulatory molecules (e.g., IFNγ and IDO). Interestingly, inhibition of NF-kB signaling decreased the TLR3-activated IFNγ but increased the TLR3-activated IDO expression, suggesting the multiple pathways in the inductive mechanism. Our finding supports the concept that activated TLR3 could encourage the stem cell and immunosuppressive properties of PDLSCs. Since immunosuppressive properties of stem cells could support tissue healing and regeneration, activation of TLR3 in PDL cells may trigger the effective PDL tissue regeneration.