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...
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doaj-62ac5584547a4938b5aea5d686aa41d92020-11-25T02:39:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-03-011110.3389/fimmu.2020.00438506821Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic CellsWaqas Azeem0Waqas Azeem1Ragnhild Maukon Bakke2Silke Appel3Silke Appel4Anne Margrete Øyan5Anne Margrete Øyan6Karl-Henning Kalland7Karl-Henning Kalland8Karl-Henning Kalland9Department of Microbiology, Haukeland University Hospital, Helse Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Microbiology, Haukeland University Hospital, Helse Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayBroegelmann Research Laboratory, University of Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Immunology and Transfusion Medicine, Haukeland University Hospital, Helse Bergen, Bergen, NorwayDepartment of Microbiology, Haukeland University Hospital, Helse Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayNorway Centre for Cancer Biomarkers, University of Bergen, Bergen, NorwayThe 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.https://www.frontiersin.org/article/10.3389/fimmu.2020.00438/fullmonocyte-derived dendritic cellpro-inflammatorytolerogenicimmunotherapybeta-catenin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Waqas Azeem Waqas Azeem Ragnhild Maukon Bakke Silke Appel Silke Appel Anne Margrete Øyan Anne Margrete Øyan Karl-Henning Kalland Karl-Henning Kalland Karl-Henning Kalland |
spellingShingle |
Waqas Azeem Waqas Azeem Ragnhild Maukon Bakke Silke Appel Silke Appel Anne Margrete Øyan Anne Margrete Øyan Karl-Henning Kalland Karl-Henning Kalland Karl-Henning Kalland Dual Pro- and Anti-Inflammatory Features of Monocyte-Derived Dendritic Cells Frontiers in Immunology monocyte-derived dendritic cell pro-inflammatory tolerogenic immunotherapy beta-catenin |
author_facet |
Waqas Azeem Waqas Azeem Ragnhild Maukon Bakke Silke Appel Silke Appel Anne Margrete Øyan Anne Margrete Øyan Karl-Henning Kalland Karl-Henning Kalland Karl-Henning Kalland |
author_sort |
Waqas Azeem |
title |
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_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_sort |
dual pro- and anti-inflammatory features of monocyte-derived dendritic cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-03-01 |
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. |
topic |
monocyte-derived dendritic cell pro-inflammatory tolerogenic immunotherapy beta-catenin |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00438/full |
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