Stem cells from human exfoliated deciduous teeth (SHED) are a unique postnatal stem cell population, possessing multipotent differentiation capacity and immunomodulatory properties. However, the mechanism by which SHED treat immune diseases is not fully understood. Here we show that systemic transplantation of SHED via the tail vein ameliorates ovariectomy (OVX)-induced osteopenia by reducing T-helper 1 (Th1) and T-helper 17 (Th17) cell numbers in the recipient OVX mice. Mechanistically, SHED transplantation induces activated T-cell apoptosis in OVX mice via Fas ligand (FasL)-mediated Fas pathway activation, leading to up-regulation of regulatory T-cells (Tregs) and down-regulation of Th1 and Th17 cells. This SHED-mediated immunomodulation rescues OVX-induced impairment of bone marrow mesenchymal stem cells (BMMSCs) and activation of osteoclastogenesis, resulting in increased bone mass. In summary, SHED-mediated T-cell apoptosis via a FasL/Fas pathway results in immune tolerance and ameliorates the osteopenia phenotype in OVX mice.

Dental pulp stem cells (DPSCs) possess immunoregulatory properties, but the underlying mechanism is not fully understood. Here we showed that DPSCs were capable of inducing activated T-cell apoptosis in vitro and ameliorating inflammatory-related tissue injuries when systemically infused into a murine colitis model. Mechanistically, DPSC-induced immunoregulation was associated with the expression of Fas ligand (FasL), a transmembrane protein that plays an important role in inducing the Fas apoptotic pathway. Knockdown of FasL expression by siRNA in DPSCs reduced their capacity to induce T-cell apoptosis in vitro and abolished their therapeutic effects in mice with colitis. However, the expression level of FasL did not affect either DPSC proliferation rate or multipotent differentiation potential. In summary, FasL governs the immunoregulatory property of DPSCs in the context of inducing T-cell apoptosis.

Our findings suggest that these VDR polymorphisms are associated with 25(OH)D levels and that there exists a genetic predisposition for vitiligo in the Chinese population.