Human monocyte-derived dendritic cells stimulated with specific nondigestible oligosaccharides mimicking the functionality of breast milk oligosaccharides induce CD4 + Foxp3high T cells

Non-digestible oligosaccharides (NDO) alone or in combination with lactic acid bacteria (LAB) have been shown to harbor preventive effects towards immuneregulatory disorders like allergies. Therefore it is current practice to apply LAB and NDO derived from bovine milk (galacto-oligosaccharides) and plants (fructooligosaccharides) mimicking the functionality and molecular size of human milk oligosaccharides as a supplement in infant formulas. In previous studies we revealed direct effects of these NDO mixtures alone or in combination with certain LAB on human monocyte-derived dendritic cells (MoDC), showing an enhancing effect of NDO and LAB on IL-10 release by MoDC. The aim of this study was to further investigate and confirm a possible induction of foxp3high regulatory T cells by NDO and/or LAB- stimulated MoDC. Immature human MoDC prepared from peripheral blood of healthy non-atopic volunteers were screened in vitro after stimulation with specific NDO mixtures in the presence or absence of different LAB strains. Cytokine release by MoDC was analyzed after 24 h in cell-free supernatants by luminex-based assay and ELISA. To investigate the resulting T cell response, stimulated MoDC were further co-incubated with naïve T cells in allogenic stimulation assays and intracellular Foxp3 expression was assessed. NDO and LAB exert a significant enhancing effect on anti-inflammatory IL-10 secretion by MoDC, while no ability to increase pro-inflammatory IL-12p70 production was observed. T cells induced by these MoDC show a regulatory T cell phenotype characterized by Foxp3 expression. These results indicate immune-regulatory properties of the investigated NDO in the presence or absence of LAB in vitro. The tested combinations might represent a useful dietary supplement for the maintenance of intestinal hemostasis via the induction of regulatory T cells and therefore could be considered as allergy preventing ingredients in food.