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Dimethyl fumarate therapy reduces memory T cells and the CNS migration potential in patients with multiple sclerosis

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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.

Original languageEnglish
JournalMultiple Sclerosis and Related Disorders
Volume37
Pages (from-to)101451
ISSN2211-0348
DOIs
Publication statusPublished - Jan 2020

    Research areas

  • Adult, Cell Proliferation/drug effects, Cohort Studies, Cytokines/drug effects, Dimethyl Fumarate/pharmacology, Female, Fumarates/pharmacology, Humans, Immunologic Factors/pharmacology, Inflammation/blood, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting/blood, T-Lymphocytes/drug effects, Young Adult

ID: 61516620