Abstract
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.
Highlights
Dendritic cells (DCs) are the most efficient antigen-presenting cells of the immune system and play a vital role in initiating the adaptive immune response and maintaining tolerance to self-antigens [1]
Immature DCs continually search their environment for antigens, while mature DCs migrate to the lymph nodes and present processed antigens on their major histocompatibility (MHC) molecules to T cells
Three different types of DCs have been considered in peripheral blood, plasmacytoid DCs and classical or conventional DC type 1 and type 2 [2,3,4]
Summary
Dendritic cells (DCs) are the most efficient antigen-presenting cells of the immune system and play a vital role in initiating the adaptive immune response and maintaining tolerance to self-antigens [1]. Immature DCs continually search their environment for antigens, while mature DCs migrate to the lymph nodes and present processed antigens on their major histocompatibility (MHC) molecules to T cells. DCs comprise less than 1% of circulating blood leukocytes, and for this reason, most DC-based therapies have relied on DCs generated in vitro from the more plentiful. Dendritic Cell Inflammatory Features blood monocytes [reviewed in [2,3,4, 7, 8]]. Monocyte-derived DCs (moDCs) are able to activate the immune system, but it may be anticipated that there is a considerable potential for the generation of more potent and robust DCs for cancer therapy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
