Selective S1P Receptor Modulation in Multiple Sclerosis Alters CXCL13:CXCR5-Associated Immune Activities Without
Andrea Harrer1,2, Richard F Radlberger3, Beate Buchegger4
1Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, Centre for Cognitive Neuroscience, EpiCARE, Salzburg, Austria. a.harrer@salk.at.
Neurology and Therapy
|October 8, 2025
Summary
Ozanimod, a selective sphingosine-1-phosphate receptor modulator, reduces CXCL13:CXCR5 axis activity in multiple sclerosis (MS) patients. This modulation preserves anti-viral immunity, particularly through CD8+ T cells, suggesting a favorable safety profile for MS treatment.
Area of Science:
- Immunology
- Neuroscience
- Pharmacology
Background:
- Sphingosine-1-phosphate receptor (S1PR) modulators are used for multiple sclerosis (MS).
- Non-selective S1PR modulators carry infection risks.
- The CXCL13:CXCR5 axis is implicated in MS inflammation and protective immunity.
Purpose of the Study:
- To investigate if selective S1PR modulation with ozanimod affects the CXCL13:CXCR5 axis in MS patients.
- To assess the impact of ozanimod on anti-viral immune responses during the SARS-CoV-2 pandemic.
Main Methods:
- An observational study of 20 MS patients on ozanimod and 10 healthy controls over 1 year.
- Measurement of CXCR5+ T and B cells, serum CXCL13, and anti-SARS-CoV-2 immune responses at 3-month intervals.
Main Results:
- Ozanimod treatment decreased CXCR5+ lymphocyte counts and serum CXCL13 levels.
- Anti-SARS-CoV-2 antibody and T cell responses were maintained after vaccination/infection.
- A shift in SARS-CoV-2-reactive T cells from CD4+ to CD8+ was observed in ozanimod-treated patients.
Conclusions:
- Selective S1PR modulation with ozanimod impacts the CXCL13:CXCR5 axis, potentially reducing MS-related inflammation.
- Anti-viral immune defense appears preserved, with CD8+ T cells possibly compensating for CD4+ T cell changes.
- Immunological findings suggest a favorable safety and efficacy profile for ozanimod in MS, applicable to other viral infections.
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