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Multiple Sclerosis Treatments Affect Monocyte-Derived Microvesicle Production
Maria Blonda1, Antonella Amoruso1, Roberta Grasso1
1Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Abstract:
Microvesicles (MVs) are released by immune cells especially of the myeloid lineage upon stimulation with ATP on its cognate receptor P2X7, both in physiological and pathological conditions. In multiple sclerosis (MS) the role of MVs remains little investigated. We aimed to compare the release of MVs in peripheral blood monocytes from MS patients with healthy donors (HDs) and to see how current MS treatment may affect such a production. We also assessed the treatment effect on M1 and M2 monocyte polarization and on the inflammasome components. Spectrophotometric quantification was performed to compare monocyte-derived MVs from 20 untreated relapsing-remitting MS patients and 20 HDs and to evaluate the effect of different treatments. Subgroups of nine interferon-beta and of five teriflunomide-treated MS patients were evaluated at baseline and after 2, 6, and 12 months of treatment. Six MS patients taking Fingolimod, after switching from a first-line therapy, were included in the study and analyzed only at 12 months of treatment. MVs analysis revealed that monocytes from MS patients produced vesicles in higher amounts than controls. All treatments reduced vesicle production but only teriflunomide was associated with a downregulation of purinergic P2X7 receptor and inflammasome components expression. The therapies modulated mRNA expression of both M1 and M2 monocyte markers. Our results, suggesting new molecular targets for drugs currently used in MS, may potentially provide useful novel evidence to approach the disease.
Insights
Monocytes from multiple sclerosis (MS) patients release more microvesicles (MVs) than healthy donors. Current MS therapies reduce MV production, with teriflunomide uniquely downregulating key inflammatory markers.
Area of Science:
- Immunology
- Neuroscience
- Cell Biology
Background:
- Microvesicles (MVs) are released by myeloid immune cells, particularly upon ATP stimulation via the P2X7 receptor.
- The role of MVs in multiple sclerosis (MS) pathogenesis is not well understood.
- Monocyte polarization (M1/M2) and inflammasome activity are implicated in MS.
Purpose of the Study:
- To compare MV release from monocytes of MS patients versus healthy donors (HDs).
- To investigate the impact of current MS treatments (interferon-beta, teriflunomide, fingolimod) on MV production.
- To assess treatment effects on monocyte polarization and inflammasome components.
Main Methods:
- Spectrophotometric quantification of monocyte-derived MVs.
- Comparison of MV release between 20 untreated MS patients and 20 HDs.
- Longitudinal analysis of MV production, P2X7 receptor, inflammasome components, and M1/M2 markers in treated MS patients.
Main Results:
- Monocytes from MS patients exhibited significantly higher MV production compared to HDs.
- All evaluated MS therapies reduced MV production.
- Teriflunomide treatment was associated with decreased P2X7 receptor and inflammasome component expression.
- MS therapies modulated the mRNA expression of both M1 and M2 monocyte markers.
Conclusions:
- MS patients show increased MV release from monocytes, suggesting a role in disease pathophysiology.
- Current MS treatments, particularly teriflunomide, can reduce MV production and associated inflammatory markers.
- These findings highlight potential novel therapeutic targets and mechanisms of action for existing MS drugs.
