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Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release
Allergy is becoming a rapidly increasing problem worldwide, and in vitro models are frequently used to study the mechanisms behind the different types of allergic response. The dendritic cell (DC)–T-cell model can be used to study sensitization. However, lipopolysaccharide (LPS) is often used to mat...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212991/ https://www.ncbi.nlm.nih.gov/pubmed/32431702 http://dx.doi.org/10.3389/fimmu.2020.00748 |
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author | Hoppenbrouwers, Tamara Fogliano, Vincenzo Garssen, Johan Pellegrini, Nicoletta Willemsen, Linette E. M. Wichers, Harry J. |
author_facet | Hoppenbrouwers, Tamara Fogliano, Vincenzo Garssen, Johan Pellegrini, Nicoletta Willemsen, Linette E. M. Wichers, Harry J. |
author_sort | Hoppenbrouwers, Tamara |
collection | PubMed |
description | Allergy is becoming a rapidly increasing problem worldwide, and in vitro models are frequently used to study the mechanisms behind the different types of allergic response. The dendritic cell (DC)–T-cell model can be used to study sensitization. However, lipopolysaccharide (LPS) is often used to maturate the DCs, but it gives rise to a DC1 phenotype, whereas Th2-driven inflammatory diseases such as allergy are characterized by the involvement of the DC2 phenotype. Our aim was to create a DC2–T-cell human model (human moDC2s) to study in vitro sensitization and validate the model using polyunsaturated fatty acids (PUFAs) that were previously shown to have immunomodulatory properties. We found that the generated DC2s expressed OX40L and drove naive T-cells into IL-13 production of CD4(+) effector T-cells. In line with in vivo findings, n−3 long-chain (LC)PUFA docosahexaenoic acid (DHA) effectively decreased the DC2's surface expression of OX40L, as well as the IL-12p40 and IL-23 cytokine production by DC2s and subsequently lowered IL-13 production by DC2-induced effector T-cells. Similar cytokine production effects were found with eicosapentaenoic acid (EPA) and arachidonic acid (AA), whereas linoleic acid (LA) increased OX40L surface expression and subsequent T-cell-derived IL-13/IFNγ ratios, suggesting an increased risk of allergy development. Altogether, these data show that human moDC2s are able to induce Th2-type IL-13 secretion by T-cell differentiated in the presence of these DC2s and that this model can be differentially modulated by PUFAs. These results are in line with previous in vivo studies using PUFAs, indicating that this model may be of use to predict in vivo outcomes. |
format | Online Article Text |
id | pubmed-7212991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72129912020-05-19 Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release Hoppenbrouwers, Tamara Fogliano, Vincenzo Garssen, Johan Pellegrini, Nicoletta Willemsen, Linette E. M. Wichers, Harry J. Front Immunol Immunology Allergy is becoming a rapidly increasing problem worldwide, and in vitro models are frequently used to study the mechanisms behind the different types of allergic response. The dendritic cell (DC)–T-cell model can be used to study sensitization. However, lipopolysaccharide (LPS) is often used to maturate the DCs, but it gives rise to a DC1 phenotype, whereas Th2-driven inflammatory diseases such as allergy are characterized by the involvement of the DC2 phenotype. Our aim was to create a DC2–T-cell human model (human moDC2s) to study in vitro sensitization and validate the model using polyunsaturated fatty acids (PUFAs) that were previously shown to have immunomodulatory properties. We found that the generated DC2s expressed OX40L and drove naive T-cells into IL-13 production of CD4(+) effector T-cells. In line with in vivo findings, n−3 long-chain (LC)PUFA docosahexaenoic acid (DHA) effectively decreased the DC2's surface expression of OX40L, as well as the IL-12p40 and IL-23 cytokine production by DC2s and subsequently lowered IL-13 production by DC2-induced effector T-cells. Similar cytokine production effects were found with eicosapentaenoic acid (EPA) and arachidonic acid (AA), whereas linoleic acid (LA) increased OX40L surface expression and subsequent T-cell-derived IL-13/IFNγ ratios, suggesting an increased risk of allergy development. Altogether, these data show that human moDC2s are able to induce Th2-type IL-13 secretion by T-cell differentiated in the presence of these DC2s and that this model can be differentially modulated by PUFAs. These results are in line with previous in vivo studies using PUFAs, indicating that this model may be of use to predict in vivo outcomes. Frontiers Media S.A. 2020-05-04 /pmc/articles/PMC7212991/ /pubmed/32431702 http://dx.doi.org/10.3389/fimmu.2020.00748 Text en Copyright © 2020 Hoppenbrouwers, Fogliano, Garssen, Pellegrini, Willemsen and Wichers. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Hoppenbrouwers, Tamara Fogliano, Vincenzo Garssen, Johan Pellegrini, Nicoletta Willemsen, Linette E. M. Wichers, Harry J. Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release |
title | Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release |
title_full | Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release |
title_fullStr | Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release |
title_full_unstemmed | Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release |
title_short | Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release |
title_sort | specific polyunsaturated fatty acids can modulate in vitro human modc2s and subsequent th2 cytokine release |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212991/ https://www.ncbi.nlm.nih.gov/pubmed/32431702 http://dx.doi.org/10.3389/fimmu.2020.00748 |
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