Exposure of intestinal epithelial cells to short- and long-chain fructo-oligosaccharides and CpG oligodeoxynucleotides enhances peanut-specific T Helper 1 polarization
| Autor: | Simone M. Hayen, Henny G. Otten, Saskia A. Overbeek, André C. Knulst, Johan Garssen, Linette E. M. Willemsen |
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| Přispěvatelé: | Afd Pharmacology, Pharmacology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Arachis medicine.medical_treatment Oligosaccharides Epithelial cells Lymphocyte Activation immunomodulation Neutralization 0302 clinical medicine Immunology and Allergy Receptor Original Research Chemistry non-digestible oligosaccharides Middle Aged Phenotype Interleukin-10 T cell polarization Intestines Cytokine Oligodeoxyribonucleotides CpG site Female HT29 Cells Adult lcsh:Immunologic diseases. Allergy Adolescent CpG Oligodeoxynucleotide Immunology Peripheral blood mononuclear cell Immunomodulation Young Adult 03 medical and health sciences medicine Humans allergen-specific Immunotherapy Allergens Th1 Cells Non-digestible oligosaccharides co-culture Molecular biology Coculture Techniques epithelial cells 030104 developmental biology Allergen-specific Co-culture lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, 9(MAY). Frontiers Media S. A. Frontiers in Immunology, 9. Frontiers Media S.A. Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | Background: 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. Methods: 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. Results: 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
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