PMID- 33658990 OWN - NLM STAT- MEDLINE DCOM- 20210616 LR - 20210616 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Fructo-Oligosaccharides Modify Human DC Maturation and Peanut-Induced Autologous T-Cell Response of Allergic Patients In Vitro. PG - 600125 LID - 10.3389/fimmu.2020.600125 [doi] LID - 600125 AB - BACKGROUND: Dendritic 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. OBJECTIVE: This 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. METHODS: CD14(+) 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. RESULTS: Expression 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. CONCLUSION: Only 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. CI - Copyright (c) 2021 Hayen, Knulst, Garssen, Otten and Willemsen. FAU - Hayen, Simone M AU - Hayen SM AD - Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. AD - Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands. FAU - Knulst, Andre C AU - Knulst AC AD - Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. FAU - Garssen, Johan AU - Garssen J AD - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands. AD - Department of Immunology, Nutricia Research B.V., Utrecht, Netherlands. FAU - Otten, Henny G AU - Otten HG AD - Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands. FAU - Willemsen, Linette E M AU - Willemsen LEM AD - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210215 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Immunologic Factors) RN - 0 (Oligosaccharides) RN - 0 (Plant Extracts) RN - 0 (fructooligosaccharide) SB - IM MH - Adolescent MH - Adult MH - Arachis/*chemistry MH - Cells, Cultured MH - Dendritic Cells/*immunology/pathology MH - Female MH - Humans MH - Immunologic Factors/immunology/*pharmacology MH - Male MH - Middle Aged MH - Oligosaccharides/immunology/*pharmacology MH - Peanut Hypersensitivity/*immunology/pathology MH - Plant Extracts/chemistry/*pharmacology MH - T-Lymphocytes, Helper-Inducer/*immunology/pathology PMC - PMC7917053 OTO - NOTNLM OT - T cells OT - dendritic cells OT - immunomodulation OT - non-digestible oligosaccharides OT - peanut allergy COIS- JG is employed at the Utrecht University and at Nutricia Research B.V. LW works at the Pharmacology division of the Utrecht University within a strategic alliance with Nutricia Research B.V. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/03/05 06:00 MHDA- 2021/06/17 06:00 PMCR- 2020/01/01 CRDT- 2021/03/04 05:54 PHST- 2020/08/28 00:00 [received] PHST- 2020/12/24 00:00 [accepted] PHST- 2021/03/04 05:54 [entrez] PHST- 2021/03/05 06:00 [pubmed] PHST- 2021/06/17 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.600125 [doi] PST - epublish SO - Front Immunol. 2021 Feb 15;11:600125. doi: 10.3389/fimmu.2020.600125. eCollection 2020.