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

•Dimethyl fumarate reduces the prevalence of circulating proinflammatory memory T cells.•Dimethyl fumarate reduces recruitment of CD4+ T cells to the cerebrospinal fluid.•Monomethyl fumarate dampens T cell proliferation.•Monomethyl fumarate reduces the proinflammatory cytokine profile of CD4+ T cell...

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Veröffentlicht in:Multiple sclerosis and related disorders 2020-01, Vol.37, p.101451-101451, Article 101451
Hauptverfasser: Holm Hansen, Rikke, Højsgaard Chow, Helene, Christensen, Jeppe Romme, Sellebjerg, Finn, von Essen, Marina Rode
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Sprache:eng
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Zusammenfassung:•Dimethyl fumarate reduces the prevalence of circulating proinflammatory memory T cells.•Dimethyl fumarate reduces recruitment of CD4+ T cells to the cerebrospinal fluid.•Monomethyl fumarate dampens T cell proliferation.•Monomethyl fumarate reduces the proinflammatory cytokine profile of CD4+ T cells. 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. In this study we evaluate the therapeutic effects of DMF on T cell subpopulations, their CNS migration potential and effector functions. Blood and CSF from untreated and DMF-treated patients with RRMS and healthy donors were analyzed by flow cytometry. 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. 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.
ISSN:2211-0348
2211-0356
DOI:10.1016/j.msard.2019.101451