Category: Autoimmune neurologic diseases
Background: Dimethyl fumarate (DMF) is a disease modifying therapy used for patients with relapsing-remitting multiple sclerosis (RRMS). T cells are major contributors to the pathogenesis of RRMS, where they regulate the inflammatory immune response and participate in infiltration and lesion development in the CNS. The impact of DMF on T cell subpopulations, their CNS trans-migration potential and effector functions remains unsolved.
Objectives: We evaluated the effects of DMF on T cell subsets, their CNS trans-migration potential and their effector functions.
Methods: Blood and cerebrospinal fluid (CSF) cells from untreated and DMF-treated patients with RRMS and healthy donors were analyzed by flow cytometry.
Results: We found that DMF reduced the prevalence of circulating memory T cells. This reduction was observed in proinflammatory CD4+ and CD8+ T cell subsets whereas regulatory T cells were unaffected. Furthermore, DMF reduced the frequency of peripheral CD4+ T cells expressing CNS-homing markers. Additionally, we found a reduced recruitment of CD4+ T cells but not CD8+ T cells to the CSF. We also found that monomethyl fumarate (MMF), the primary metabolite of DMF, dampened T cell proliferation in vitro and reduced the frequency of TNFα, IL-17 and IFN-γ producing T cells.
RIkke Hansen– Cand. Scient. PhD stud., Danish Multiple Sclerosis Center, department of neurology, Copenhagen university hospital, Rigshospitalet
Helene Højsgaard Chow– Danish multiple sclerosis center, department of neurology, copenhagen university hospital, rigshospitalet
Jeppe Romme Christensen– Danish multiple sclerosis center, department of neurology, copenhagen university hospital, rigshospitalet
Finn Sellebjerg– Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet
Marina Rode von Essen– Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet