Rikke Holm Hansen1, Helene Højsgaard Chow2, Jeppe Romme Christensen2, Finn Sellebjerg2, Marina Rode von Essen2. 1. The Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Valdemar Hansens Vej 17, 2600 Glostrup, Denmark. Electronic address: rikke.holm.hansen@regionh.dk. 2. The Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Valdemar Hansens Vej 17, 2600 Glostrup, Denmark.
Abstract
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.
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.
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