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A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes
Published on: April 11, 2025
785
Induction of Tolerogenic Dendritic Cells by a Noncoding Oligonucleotide
Kahkashan Kamal1, James Trumbo1, Elina Richardsdotter-Andersson2
1Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
European Journal of Immunology
|October 27, 2025
Summary
Tolerogenic dendritic cells (tolDCs) were generated from monocytes using a novel single-stranded oligonucleotide (ssON). These ssON-modified tolDCs effectively dampen T cell responses and show potential for cell therapy applications.
Area of Science:
- Immunology
- Cell Biology
- Biotechnology
Background:
- Tolerogenic dendritic cells (tolDCs) are crucial for modulating immune responses.
- Current methods for generating tolDCs face challenges in efficiency and viability.
- Previous research indicated ssONs can recruit immunomodulatory monocytic cells in vivo.
Purpose of the Study:
- To investigate the effect of immunomodulatory noncoding single-stranded oligonucleotides (ssON) on human monocyte differentiation into dendritic cells (moDC).
- To characterize the phenotype and function of ssON-modified moDCs.
- To explore the potential of ssON-moDCs for cell therapy.
Main Methods:
- Human monocytes were differentiated into dendritic cells (moDC) using IL-4, GM-CSF, and ssON.
- Phenotypic analysis included CD1a and PD-L1 expression.
- Functional assays assessed T cell stimulation and regulatory T cell induction.
- Transcriptomic analysis and PPAR-γ pathway investigation were performed.
Main Results:
- ssON-moDC exhibited upregulated CD1a and PD-L1 expression.
- Differentiation with ssON induced transcriptomic changes overlapping with Vitamin D3-treated moDCs.
- ssON-moDCs showed reduced alloreactive T cell stimulation and promoted CD4+FoxP3+CD25+ T cell induction.
- Evidence suggests a role for PPAR-γ in ssON-moDC generation.
Conclusions:
- Monocytes differentiated with IL-4, GM-CSF, and ssON yield cells with tolDC characteristics.
- ssON-modified moDCs possess potent immune-dampening capabilities.
- These findings highlight ssON-moDCs as a promising candidate for cell-based immunotherapies.
