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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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@article{9431ff442298420e9fa3c3324cb43cec,
title = "Dimethyl fumarate therapy reduces memory T cells and the CNS migration potential in patients with multiple sclerosis",
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.",
keywords = "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",
author = "{Holm Hansen}, Rikke and {H{\o}jsgaard Chow}, Helene and Christensen, {Jeppe Romme} and Finn Sellebjerg and {von Essen}, {Marina Rode}",
note = "Copyright {\textcopyright} 2019 Elsevier B.V. All rights reserved.",
year = "2020",
month = jan,
doi = "10.1016/j.msard.2019.101451",
language = "English",
volume = "37",
pages = "101451",
journal = "Multiple Sclerosis and Related Disorders",
issn = "2211-0348",
publisher = "Elsevier",

}

RIS

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

N1 - Copyright © 2019 Elsevier B.V. All rights reserved.

PY - 2020/1

Y1 - 2020/1

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.

KW - Adult

KW - Cell Proliferation/drug effects

KW - Cohort Studies

KW - Cytokines/drug effects

KW - Dimethyl Fumarate/pharmacology

KW - Female

KW - Fumarates/pharmacology

KW - Humans

KW - Immunologic Factors/pharmacology

KW - Inflammation/blood

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis, Relapsing-Remitting/blood

KW - T-Lymphocytes/drug effects

KW - Young Adult

U2 - 10.1016/j.msard.2019.101451

DO - 10.1016/j.msard.2019.101451

M3 - Journal article

C2 - 31675639

VL - 37

SP - 101451

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

ER -

ID: 61516620