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Updated: May 11, 2026
Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Wnt5a inhibits human monocyte-derived myeloid dendritic cell generation
C Bergenfelz1, H Janols, M Wullt
1Center for Molecular Pathology, Skåne University Hospital, Lund University, Malmö, Sweden.
Abstract:
Wnt5a is a non-canonical Wnt protein that is expressed at elevated levels in inflammatory conditions. Its role in inflammation remains unclear, although it is known that Wnt5a is expressed at a higher level in monocyte-derived myeloid dendritic cells (Mo-mDCs) than in monocytes and macrophages. The function of Wnt5a in dendritic cells (DCs) remains relatively unexplored. Here, we found that under Mo-mDC culture conditions, Wnt5a inhibited the generation of CD14(⁺/low) Mo-mDCs while promoting the generation of CD14⁺/⁺⁺ CD16⁺ monocytes. We could further show that stimulation of monocytes with rWnt5a induced a rapid IL-6 production and that the rWnt5a treated Mo-mDC differentiation was restored upon blocking of IL-6. Also, conditioned media from Wnt5a stimulated human breast cancer cells producing IL-6, specifically inhibited Mo-mDC differentiation. These observations are strengthened by our finding that patients with sepsis, a disease involving elevated Wnt5a and IL-6 levels, also showed a significant increase in the CD14⁺ CD16⁺⁺/CD14⁺/⁺⁺ CD16⁺ monocyte populations, which was accompanied by a significant decrease in circulating mDCs. We finally show that under typical Mo-mDC culture conditions, monocytes isolated from patients with sepsis as compared to healthy controls, preferentially differentiated into CD14CD14⁺/⁺⁺ HLA-DR⁺⁺ cells. We suggest that Wnt5a is a possible candidate mediator for the CD14⁺/⁺⁺ CD16⁺ monocyte accumulation seen in patients with infectious disease and cancer.
Insights
Wnt5a protein inhibits dendritic cell generation and promotes specific monocyte populations during inflammation. This Wnt5a-induced effect is mediated by IL-6, impacting conditions like sepsis and cancer.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Wnt5a is upregulated in inflammatory conditions.
- Wnt5a expression is higher in monocyte-derived myeloid dendritic cells (Mo-mDCs) than in monocytes or macrophages.
- The specific function of Wnt5a in dendritic cells (DCs) is not well understood.
Purpose of the Study:
- To investigate the role of Wnt5a in the differentiation of monocytes and dendritic cells.
- To explore the mechanism by which Wnt5a influences immune cell populations in inflammatory settings.
Main Methods:
- Monocyte-derived myeloid dendritic cell (Mo-mDC) cultures.
- Recombinant Wnt5a (rWnt5a) stimulation of monocytes.
- Interleukin-6 (IL-6) level measurements and blocking experiments.
- Analysis of monocyte and dendritic cell populations in sepsis patients.
Main Results:
- Wnt5a inhibited CD14(low) Mo-mDC generation while promoting CD14⁺/⁺⁺ CD16⁺ monocyte formation.
- rWnt5a induced rapid IL-6 production in monocytes; blocking IL-6 restored Mo-mDC differentiation.
- Conditioned media from Wnt5a-stimulated cancer cells, containing IL-6, also inhibited Mo-mDC differentiation.
- Sepsis patients exhibited increased CD14⁺ CD16⁺⁺/CD14⁺/⁺⁺ CD16⁺ monocytes and decreased circulating mDCs, correlating with elevated Wnt5a and IL-6.
- Sepsis-derived monocytes preferentially differentiated into CD14⁺/⁺⁺ HLA-DR⁺⁺ cells under Mo-mDC culture conditions.
Conclusions:
- Wnt5a plays a significant role in modulating monocyte and dendritic cell differentiation during inflammation.
- IL-6 is a key mediator of Wnt5a's inhibitory effect on Mo-mDC generation.
- Wnt5a may contribute to the accumulation of CD14⁺/⁺⁺ CD16⁺ monocytes observed in infectious diseases and cancer.
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