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Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells
The transcription factor β-catenin is able to induce tolerogenic/anti-inflammatory features in different types of dendritic cells (DCs). Monocyte-derived dendritic cells (moDCs) have been widely used in dendritic cell-based cancer therapy, but so far with limited clinical efficacy. We wanted to inve...
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/PMC7120039/ https://www.ncbi.nlm.nih.gov/pubmed/32292402 http://dx.doi.org/10.3389/fimmu.2020.00438 |
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author | Azeem, Waqas Bakke, Ragnhild Maukon Appel, Silke Øyan, Anne Margrete Kalland, Karl-Henning |
author_facet | Azeem, Waqas Bakke, Ragnhild Maukon Appel, Silke Øyan, Anne Margrete Kalland, Karl-Henning |
author_sort | Azeem, Waqas |
collection | PubMed |
description | The transcription factor β-catenin is able to induce tolerogenic/anti-inflammatory features in different types of dendritic cells (DCs). Monocyte-derived dendritic cells (moDCs) have been widely used in dendritic cell-based cancer therapy, but so far with limited clinical efficacy. We wanted to investigate the hypothesis that aberrant differentiation or induction of dual pro- and anti-inflammatory features may be β-catenin dependent in moDCs. β-catenin was detectable in both immature and lipopolysaccharide (LPS)-stimulated DCs. The β-catenin inhibitor ICG-001 dose-dependently increased the pro-inflammatory signature cytokine IL-12p70 and decreased the anti-inflammatory signature molecule IL-10. The β-catenin activator 6-bromoindirubin-3′-oxime (6-BIO) dose-dependently increased total and nuclear β-catenin, and this was associated with decreased IL-12p70, increased IL-10, and reduced surface expression of activation markers, such as CD80 and CD86, and increased expression of inhibitory markers, such as PD-L1. 6-BIO and ICG-001 competed dose-dependently regarding these features. Genome-wide mRNA expression analyses further underscored the dual development of pro- and anti-inflammatory features of LPS-matured moDCs and suggest a role for β-catenin inhibition in production of more potent therapeutic moDCs. |
format | Online Article Text |
id | pubmed-7120039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-71200392020-04-14 Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells Azeem, Waqas Bakke, Ragnhild Maukon Appel, Silke Øyan, Anne Margrete Kalland, Karl-Henning Front Immunol Immunology The transcription factor β-catenin is able to induce tolerogenic/anti-inflammatory features in different types of dendritic cells (DCs). Monocyte-derived dendritic cells (moDCs) have been widely used in dendritic cell-based cancer therapy, but so far with limited clinical efficacy. We wanted to investigate the hypothesis that aberrant differentiation or induction of dual pro- and anti-inflammatory features may be β-catenin dependent in moDCs. β-catenin was detectable in both immature and lipopolysaccharide (LPS)-stimulated DCs. The β-catenin inhibitor ICG-001 dose-dependently increased the pro-inflammatory signature cytokine IL-12p70 and decreased the anti-inflammatory signature molecule IL-10. The β-catenin activator 6-bromoindirubin-3′-oxime (6-BIO) dose-dependently increased total and nuclear β-catenin, and this was associated with decreased IL-12p70, increased IL-10, and reduced surface expression of activation markers, such as CD80 and CD86, and increased expression of inhibitory markers, such as PD-L1. 6-BIO and ICG-001 competed dose-dependently regarding these features. Genome-wide mRNA expression analyses further underscored the dual development of pro- and anti-inflammatory features of LPS-matured moDCs and suggest a role for β-catenin inhibition in production of more potent therapeutic moDCs. Frontiers Media S.A. 2020-03-27 /pmc/articles/PMC7120039/ /pubmed/32292402 http://dx.doi.org/10.3389/fimmu.2020.00438 Text en Copyright © 2020 Azeem, Bakke, Appel, Øyan and Kalland. 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 Azeem, Waqas Bakke, Ragnhild Maukon Appel, Silke Øyan, Anne Margrete Kalland, Karl-Henning Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells |
title | Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells |
title_full | Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells |
title_fullStr | Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells |
title_full_unstemmed | Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells |
title_short | Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells |
title_sort | dual pro- and anti-inflammatory features of monocyte-derived dendritic cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120039/ https://www.ncbi.nlm.nih.gov/pubmed/32292402 http://dx.doi.org/10.3389/fimmu.2020.00438 |
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