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.
SUMMARY BackgroundSerum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in various autoimmune and liver diseases.
In addition to their potential for replacing damaged and diseased tissues by differentiating into tissuespecific cells, mesenchymal stem cells (MSCs) have been found to interact closely with immune cells, such as lymphocytes. In this review, we will discuss current research regarding the immunomodulatory properties of MSCs and the effects of lymphocytes on MSCs. We will suggest how these findings could be translated to potential clinical treatment. MSCs can regulate immune response by inducing activated T-cell apoptosis through the FAS ligand (FASL)/FAS-mediated death pathway via cell-cell contact, leading to up-regulation of regulatory T-cells (Tregs), which ultimately results in immune tolerance. Conversely, lymphocytes can impair survival and osteogenic differentiation of implanted MSCs by secreting the pro-inflammatory cytokines IFN-γ and TNF-α and/or through the FASL/FAS-mediated death pathway, thereby negatively affecting MSC-mediated tissue regeneration. One novel strategy to improve MSC-based tissue engineering involves the reduction of IFN-γ and TNF-α concentration by systemic infusion of Tregs or local application of aspirin. Further understanding of the mechanisms underlying the interplay between lymphocytes and MSCs may be helpful in the development of promising approaches to improve cell-based regenerative medicine and immune therapies.
The currently used vaccine against tuberculosis, Bacille Calmette‐Guérin (BCG), has variable efficacy, so new vaccine development is crucial. In this study, we evaluated a recombinant vaccine prepared from non‐pathogenic Mycobacterium smegmatis (rMS) that expresses a fusion of early secreted antigenic target 6‐kDa antigen (ESAT6) and culture filtrate protein 10 (CFP10). C57BL/6 mice were immunized with the rMS expressing the ESAT6‐CFP10 fusion protein (rM.S‐e6c10) or with BCG. The mice in the rM.S‐e6c10 group had a significantly higher titre of anti‐ESAT6‐CFP10 antibodies than did animals in the BCG or saline groups. Spleen cells from rM.S‐e6c10‐immunized mice exhibited a cytotoxic response to ESAT6 and CFP10‐expressed target cells, but spleen cells from animals in the other groups did not. Levels of IFN‐γ and IL‐2 production by purified T cells from spleens were significantly higher in rM.S‐e6c10 group than in BCG group. Finally, after M. tuberculosis (MTB)‐challenged mice, dramatic reduction in the numbers of MTB colony‐forming units (CFUs) in the lungs was observed for the mice immunized with the rMS. The protective efficacy of rM.S‐e6c10 and BCG vaccination was similar based on measures of MTB burden and lung pathology. Our data indicate that the recombinant M. smegmatis vaccine expressing the ESAT6‐CFP10 fusion protein has potential in clinic application.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.