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Selective suppression of chemokine receptor CXCR3 expression by interferon-beta1a in multiple sclerosis
1The MS Clinic, Department of Neurology, University of Copenhagen, Glostrup, Denmark. torbenls@dadlnet.dk
Abstract:
We studied the expression of chemokine receptors CCR1, CCR2, CCR3, CCR5, and CXCR3 on CD4 and CD8 positive T cells, and on CD14 positive monocytes in blood from 10 patients with relapsing-remitting multiple sclerosis (MS) at initiation of interferon (IFN)-beta treatment, after 1 month and after 3 months of treatment. It was found that the expression of CXCR3 on CD4+ and CD8+ T cells was significantly reduced after 3 months of treatment. The expression of other receptors was unaltered. Since CXCR3 cells are enriched in cerebrospinal fluid (CSF), and are detected in lesion material in MS this may represent an important mode of action of interferon-beta in MS.
Insights
Interferon-beta treatment for multiple sclerosis (MS) significantly reduced CXCR3 expression on T cells. This finding suggests a key mechanism for how interferon-beta (IFN-beta) impacts MS progression.
Area of Science:
- Immunology
- Neuroimmunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Chemokine receptors play a role in immune cell trafficking in MS.
- Interferon-beta (IFN-beta) is a common treatment for relapsing-remitting MS.
Purpose of the Study:
- To investigate the effect of interferon-beta (IFN-beta) treatment on chemokine receptor expression in patients with relapsing-remitting multiple sclerosis (MS).
- To determine changes in CXCR3, CCR1, CCR2, CCR3, and CCR5 expression on T cells and monocytes during IFN-beta therapy.
Main Methods:
- Blood samples were collected from 10 relapsing-remitting MS patients at the start of IFN-beta treatment, and at 1 and 3 months.
- Flow cytometry was used to analyze the expression of chemokine receptors (CCR1, CCR2, CCR3, CCR5, CXCR3) on CD4+ T cells, CD8+ T cells, and CD14+ monocytes.
Main Results:
- A significant reduction in CXCR3 expression was observed on both CD4+ and CD8+ T cells after 3 months of IFN-beta treatment.
- Expression levels of CCR1, CCR2, CCR3, and CCR5 on T cells and monocytes remained largely unchanged throughout the treatment period.
Conclusions:
- The downregulation of CXCR3 on T cells is a potential mechanism of action for interferon-beta in treating multiple sclerosis.
- CXCR3-expressing T cells are implicated in CNS inflammation in MS, and their reduction may limit disease activity.