TY - JOUR

T1 - Dimethyl fumarate therapy reduces memory T cells and the CNS migration potential in patients with multiple sclerosis

AU - Holm Hansen, Rikke

AU - Højsgaard Chow, Helene

AU - Christensen, Jeppe Romme

AU - Sellebjerg, Finn

AU - von Essen, Marina Rode

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1016/j.msard.2019.101451

DO - 10.1016/j.msard.2019.101451

M3 - Journal article

C2 - 31675639

AN - SCOPUS:85074169266

VL - 37

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

M1 - 101451

ER -