Abstract
Non-digestible oligosaccharides promote colonization of beneficial gut bacteria and have direct immunomodulatory effects. Apical exposure of intestinal epithelial cells (IECs) to short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (scGOS/lcFOS) in a transwell co-culture model enhanced the CpG-induced (TLR-9 ligand) T helper 1 (Th1) phenotype and regulatory IL-10 response of underlying peripheral mononuclear cells (PBMCs) of healthy donors. scGOS is derived from lactose and may pose risks in severe cow's milk allergic patients, and scFOS/lcFOS may be an alternative. The goal of this study was to determine the immunomodulatory effects of scGOS/lcFOS and scFOS/lcFOS in an allergen-specific transwell co-culture model using PBMCs from peanut-allergic patients. IECs cultured on transwell filters were apically exposed to CpG, either or not in combination with oligosaccharides. These IECs were co-cultured with basolateral PBMCs of peanut-allergic patients that were either activated with aCD3/28 or peanut extract. Basolateral cytokine production and T-cell polarization were measured and the contribution of galectin-9 and the dectin-1 receptor in immune modulation were assessed. IECs exposed to CpG increased IFN-γ, IL-10, and galectin-9 production by aCD3/28-stimulated PBMCs, whereas IL-13 decreased. Both scGOS/lcFOS and scFOS/lcFOS further enhanced IFN-γ and IL-10, while suppressing IL-13 and TNF-α. In the peanut-specific model, only scFOS/lcFOS further increased IFN-γ and IL-10 production, coinciding with enhanced Th1-frequency. Expression of CRTH2 reduced after CpG exposure, and was further reduced by scFOS/lcFOS. Galectin-9 inhibitor TIM-3-Fc abrogated the additional effect of scFOS/lcFOS on peanut-specific IFN-γ production, while neutralization of the dectin-1 receptor was not effective. Epithelial exposure to scFOS/lcFOS enhanced the CpG-induced Th1 and regulatory IL-10 response in a peanut-specific co-culture model. These effects suggest scFOS/lcFOS as candidate for dietary adjunct in allergen-specific immunotherapy.
Highlights
Over the past decades, the prevalence of food allergies has increased in Western countries [1, 2]
PBMCs of these scFOS/lcFOS Affects intestinal epithelial cells (IECs)-Mediated T-Cell Polarization peanut-allergic patients were either stimulated aspecifically with aCD3/28 or peanut-specific by using a crude peanut extract. These PBMCs were co-cultured with IECs that were apically exposed to prebiotic mixtures in the presence of CpG ODN (TLR-9 ligand)
In the aspecific co-culture model with PBMCs of peanut-allergic patients, both oligosaccharide mixtures were effective in significantly enhancing IFN-γ and IL-10, while decreasing IL-13 and TNF-α production
Summary
The prevalence of food allergies has increased in Western countries [1, 2]. Harmless food proteins are recognized as being immunogenic by the immune cells of food-allergic patients, resulting in allergic sensitization In sensitized individuals, these allergens can provoke a variety of sym ptoms when ingested, ranging from itching and swelling in the mouth to anaphylaxis. These allergens can provoke a variety of sym ptoms when ingested, ranging from itching and swelling in the mouth to anaphylaxis To eliminating these food proteins from the diet, there are currently no therapies available for treating food allergies that induce sustained oral tolerance. Inducing sustained non-responsiveness or tolerance remains difficult and is often combined with severe side effects [1, 4]. The goal of this study was to determine the immunomodulatory effects of scGOS/lcFOS and scFOS/lcFOS in an allergen-specific transwell co-culture model using PBMCs from peanut-allergic patients
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