Abstract
BackgroundDendritic cells (DCs) play an important role in antigen presentation, and are an interesting target for immune-modulation in allergies. Short- and long-chain fructo-oligosaccharides (scFOS/lcFOS, FF) have immunomodulatory capacities, and may influence the outcome of DC antigen presentation.ObjectiveThis study investigated the effect of FF during DC maturation and allergen presentation using cells of peanut-allergic patients in an autologous DC-T cell assay.MethodsCD14+ and CD4+ T cells were isolated from peanut-allergic patients. CD14+ monocytes were differentiated into immature DCs (imDCs), and matured (matDCs) in the presence or absence of crude peanut-extract (CPE) and/or FF, and co-cultured in an autologous DC-T cell assay. T cell polarization, proliferation and cytokine production were measured.ResultsExpression of maturation surface molecule markers on matDCs was not affected by CPE and/or FF. By contrast, the IL-10 secretion by matDCs increased compared to imDCs, upon exposure to CPE and FF compared to CPE alone. Also the IP-10 secretion increased in CPE/FF-matDCs compared to imDC. CPE-matDCs enhanced IL-13 release in the DC-T-cell assay and Treg polarization in presence or absence of FF. CPE/FF-DCs tended to increase the Treg/Th1 and Treg/Th2 ratios compared to matDCs. The proliferation of both Treg and Th2 cells tended to increase when T cells were co-cultured with CPE-matDCs compared to matDCs, which became significant when CPE-matDCs were also exposed to FF and a same tendency was shown for Th1 proliferation.ConclusionOnly in the presence of FF, CPE-matDCs produced increased regulatory and Th1-related mediators. CPE-matDCs modified T cell polarization and proliferation, and additional exposure to FF tended to enhance Treg/Th2 and Treg/Th1 ratios instructed by CPE/FF-matDCs. However this effect was not strong enough to suppress CPE-matDCs induced IL-13 release by Th-cells. This indicates the ability of FF to modify DC maturation in the presence of an allergen supporting a more Treg/Th1 prone direction of the successive allergen specific Th2 cell response.
Highlights
Food allergies are the result of a loss of tolerance toward harmless antigens, since these antigens are recognized by the immune system as harmful
In contrast to immature Monocyte-Derived Dendritic Cells (moDCs), Dendritic cells (DCs) matured with the maturation mix showed increased expression of maturation markers CD83 and CD86 in presence or absence of combined with mg/ml peanut extract (CPE)
IL-13 production was absent in immature DCs (imDCs), and low in DCs that were solely exposed to CPE or the cytokine maturation mix
Summary
Food allergies are the result of a loss of tolerance toward harmless antigens, since these antigens are recognized by the immune system as harmful. More interest is gained toward the use of adjuvants, such as pro- and prebiotics during these forms of immunotherapy to improve existing protocols [2, 3] These adjuvants can amongst others influence the growth of beneficial bacteria in the gut, and can induce the release of beneficial mediators, such as mucosal tissue derived galectin-9 or microbial derived short-chain fatty acids (SCFAs). An example of such a prebiotic mixture is a mixture composed of short-and long-chain fructo-oligosaccharides (scFOS/lcFOS). Short- and long-chain fructooligosaccharides (scFOS/lcFOS, FF) have immunomodulatory capacities, and may influence the outcome of DC antigen presentation
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