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Dimethyl fumarate therapy reduces memory T cells and the CNS migration potential in patients with multiple sclerosis
Rikke Holm Hansen1, Helene Højsgaard Chow1, Jeppe Romme Christensen1
1The Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Valdemar Hansens Vej 17, 2600 Glostrup, Denmark.
Background:
Dimethyl fumarate (DMF) is a disease-modifying therapy for patients with relapsing-remitting multiple sclerosis (RRMS). T cells are major contributors to the pathogenesis of RRMS, where they regulate the pathogenic immune response and participate in CNS lesion development.
Objectives:
In this study we evaluate the therapeutic effects of DMF on T cell subpopulations, their CNS migration potential and effector functions.
Methods:
Blood and CSF from untreated and DMF-treated patients with RRMS and healthy donors were analyzed by flow cytometry.
Results:
DMF reduced the prevalence of circulating proinflammatory CD4+ and CD8+ memory T cells, whereas regulatory T cells were unaffected. Furthermore, DMF reduced the frequency of CD4+ T cells expressing CNS-homing markers. In coherence, we found a reduced recruitment of CD4+ but not CD8+ T cells to CSF. We also found that monomethyl fumarate dampened T cell proliferation and reduced the frequency of TNF-α, IL-17 and IFN-γ producing T cells.
Conclusion:
DMF influences the balance between proinflammatory and regulatory T cells, presumably favoring a less proinflammatory environment. DMF also reduces the CNS migratory potential of CD4+ T cells whereas CD8+ T cells are less affected. Altogether, our study suggests an anti-inflammatory effect of DMF mainly on the CD4+ T cell compartment.
Insights
Dimethyl fumarate (DMF) therapy for relapsing-remitting multiple sclerosis (RRMS) reduces proinflammatory T cells and their migration to the central nervous system (CNS). This immune modulation suggests a beneficial anti-inflammatory effect, particularly within the CD4+ T cell compartment.
Area of Science:
- Neuroimmunology
- Immunotherapy
- Multiple Sclerosis Pathogenesis
Background:
- Dimethyl fumarate (DMF) is a key disease-modifying therapy for relapsing-remitting multiple sclerosis (RRMS).
- T cells play a critical role in RRMS pathogenesis, driving immune responses and central nervous system (CNS) lesion development.
Purpose of the Study:
- To investigate the therapeutic impact of DMF on T cell subpopulations.
- To assess DMF's effects on T cell migration potential into the CNS.
- To evaluate DMF's influence on T cell effector functions.
Main Methods:
- Analysis of blood and cerebrospinal fluid (CSF) samples from RRMS patients (untreated and DMF-treated) and healthy donors.
- Flow cytometry was employed to examine T cell populations and their characteristics.
Main Results:
- DMF decreased circulating proinflammatory CD4+ and CD8+ memory T cells, while regulatory T cells remained unchanged.
- A reduction in CD4+ T cells expressing CNS-homing markers was observed with DMF treatment.
- DMF treatment led to decreased T cell proliferation and reduced production of TNF-α, IL-17, and IFN-γ.
Conclusions:
- DMF treatment shifts the T cell balance towards a less proinflammatory state.
- DMF significantly reduces the CNS migratory capacity of CD4+ T cells, with a lesser impact on CD8+ T cells.
- The study indicates that DMF exerts its anti-inflammatory effects predominantly within the CD4+ T cell compartment in RRMS.
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