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Updated: Apr 25, 2026
Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Monocyte-derived dendritic cells from HLA-B27+ axial spondyloarthritis (SpA) patients display altered functional
Introduction:
This study aimed to compare the functional capacity and gene expression profile of monocyte-derived dendritic cells (MD-DCs) in HLA-B27+ axial spondyloarthritis (SpA) patients and healthy controls.
Methods:
MD-DCs were differentiated with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) for seven days, starting from purified CD14+ monocytes and stimulated with lipopolysaccharide (LPS) for six and twenty four hours. Their capacity to stimulate allogeneic CD4+ T cells from unrelated healthy donor was tested. Transcriptomic study was performed with Affymetrix HuGene 1.0 ST microarrays. Gene expression levels were compared between patients and controls using a multivariate design under a linear model (LIMMA). Real-time quantitative PCR (qRT-PCR) was performed for validation of the most striking gene expression differences.
Results:
The stimulatory capacity of allogeneic CD4+ T cells by MD-DCs from SpA patients was decreased. Transcriptomic analysis revealed 81 genes differentially expressed in MD-DCs between SpA patients and controls (P <0.01 and fold-change <0.66 or >1.5). Four selected genes were validated by q
Rt-Pcr:
ADAMTS15, CITED2, F13A1 and SELL. Expression levels of ADAMTS15 and CITED2, encoding a metallopeptidase and a transcription factor, respectively, were inversely correlated with each other (R = 0.75, P = 0.0003). Furthermore, in silico analysis identified several genes of the Wnt signaling pathway having expression co-regulated with CITED2.
Conclusion:
This study revealed altered function and gene expression pattern in MD-DCs from HLA-B27+ axial SpA. Co-expression study showed an inverse correlation between ADAMTS15 and CITED2. Moreover, the Wnt signaling pathway appeared as deregulated in SpA MD-DCs, a finding which may be connected to Th17-driven inflammatory responses.
Insights
Monocyte-derived dendritic cells (MD-DCs) from HLA-B27+ axial spondyloarthritis (SpA) patients show reduced T cell stimulatory capacity and altered gene expression. The Wnt signaling pathway is implicated in SpA pathogenesis.
Area of Science:
- Immunology
- Genetics
- Rheumatology
Background:
- Axial spondyloarthritis (SpA) is an inflammatory disease associated with HLA-B27.
- Monocyte-derived dendritic cells (MD-DCs) play a crucial role in immune responses.
- The functional and molecular characteristics of MD-DCs in HLA-B27+ SpA remain incompletely understood.
Purpose of the Study:
- To compare the functional capacity of MD-DCs in HLA-B27+ SpA patients versus healthy controls.
- To analyze the gene expression profile of MD-DCs in HLA-B27+ SpA patients compared to controls.
- To investigate potential molecular pathways involved in MD-DC dysfunction in SpA.
Main Methods:
- MD-DCs were differentiated from CD14+ monocytes using IL-4 and GM-CSF.
- Functional capacity was assessed by allogeneic CD4+ T cell stimulation.
- Transcriptomic analysis was performed using microarrays, with validation by qRT-PCR.
Main Results:
- MD-DCs from SpA patients exhibited decreased capacity to stimulate allogeneic CD4+ T cells.
- Transcriptomic analysis identified 81 differentially expressed genes in SpA MD-DCs.
- Expression of ADAMTS15 and CITED2 was inversely correlated, and Wnt signaling pathway genes were co-regulated with CITED2.
Conclusions:
- HLA-B27+ SpA is associated with altered MD-DC function and gene expression patterns.
- An inverse correlation between ADAMTS15 and CITED2 expression was observed in SpA MD-DCs.
- Deregulation of the Wnt signaling pathway in SpA MD-DCs may contribute to Th17-driven inflammation.
