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The expression of transmembrane and soluble CXCL16 and the relation with interferon-alpha secretion in patients with
Sedat Yilmaz1, Muhammet Cinar, Aysel Pekel
1Division of Rheumatology, Gulhane School of Medicine, Ankara,Turkey. drsy75@gmail.com.
Insights
CXCL16 on plasmacytoid dendritic cells may drive high interferon-alpha in Behçet's disease. This study explored the link between CXCL16 expression and interferon-alpha secretion in Behçet's disease patients.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- CXCL16, a chemokine, is expressed on plasmacytoid dendritic cells (pDCs).
- Transmembrane CXCL16 on pDCs facilitates CpG DNA uptake, leading to high interferon-alpha (IFN-α) secretion.
- Elevated IFN-α production was previously observed in patients with Behçet's disease (BD).
Purpose of the Study:
- To investigate the relationship between IFN-α secretion and CXCL16 expression on pDCs in BD patients.
- To compare these levels with those in patients with ankylosing spondylitis (AS) and healthy controls.
Main Methods:
- Flow cytometry was used to assess CXCL16 expression on pDCs.
- ELISA measured serum levels of IFN-α and CXCL16.
- The study included 73 participants: 35 with BD, 19 with AS, and 19 controls.
Main Results:
- Serum IFN-α levels were significantly higher in BD patients compared to controls.
- Serum CXCL16 levels were elevated in both BD and AS patients compared to controls.
- A positive correlation was observed between pDC percentage and CD123+CXCL16+ cells in BD patients.
- A positive correlation was found between CD123+CXCL16+ cells and serum IFN-α in BD patients.
Conclusions:
- Transmembrane CXCL16 expression on pDCs may contribute to elevated serum IFN-α levels in Behçet's disease.
- These findings highlight a potential mechanism linking chemokine expression to autoimmune responses in BD.
Objectives:
CXCL16 is a member of CXC chemokine, which is synthesised in plasmacytoid dendritic cell as a transmembrane molecule. Transmembrane CXCL16 on plasmacytoid dendritic cell plays a role in binding, uptaking and accumulation of CpG D ODN in early endosomes rather then lysosomal vesicles, thereby causing a high level of interferon-alpha secretion. Previously, we disclosed pronounced interferon-alpha production from these cells in patients with Behçet's disease. The aim of this study was to investigate the relation between the secretion of IFN-α and the expression of CXCL16 on surface of plasmacytoid dendritic cell from patients with Behçet's disease, and compare it with patients with ankylosing spondylitis and healthy controls.
Methods:
The study population consisted of 73 cases (35 with Behçet's disease, 19 with ankylosing spondylitis and 19 controls). We investigated the expression of CXCL16 on surface of plasmacytoid dendritic cells by flow cytometry, and the serum levels of IFN-α and CXCL16 with ELISA.
Results:
Serum levels of IFN-α in patients with Behçet's disease were significantly higher than the controls (p=0.009), and than patients with ankylosing spondylitis, but not statistically significant (p=0.124). Serum levels of CXCL16 in patients with Behçet's disease and patients with ankylosing spondylitis were significantly higher than controls (p=0.009, p=0.003, respectively). We found no difference in the percentage and MFI of plasmacytoid dendritic cells and CD123+CXCL16+ cells determined by flow cytometry among the study and control groups. In patients with Behçet's disease, a positive correlation was found between the percentage of plasmacytoid dendritic cells and CD123+CXCL16+ cells (p<0.001). Furthermore, there was also a positive correlation between the percentage of plasmacytoid dendritic cells and serum levels of CXCL16 in patients with ankylosing spondylitis (p=0.001). In addition, there was a positive correlation between the percentage of CD123+CXCL16+ cells and serum levels of IFN-α in Behçet's disease group (p=0.034). We could not find any significant difference in other comparisons.
Conclusions:
We suggested that the expression of transmembrane CXCL16 on surface of plasmacytoid dendritic cell might contribute to high serum IFN-α levels seen in patients with BD.
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