Dimethyl fumarate suppresses granulocyte macrophage colony-stimulating factor-producing Th1 cells in CNS neuroinflammation.
Neurol Neuroimmunol Neuroinflamm
; 7(4)2020 07.
Article
em En
| MEDLINE
| ID: mdl-32371548
ABSTRACT
OBJECTIVE:
To study the immunomodulatory effect of dimethyl fumarate (DF) on granulocyte macrophage colony-stimulating factor (GM-CSF) production in CD4+ T cells in experimental autoimmune encephalomyelitis (EAE) and human peripheral blood mononuclear cells (PBMCs).METHODS:
We collected splenocytes and CD4+ T cells from C57BL/6 wild-type and interferon (IFN)-γ-deficient mice. For human PBMCs, venous blood was collected from healthy donors, and PBMCs were collected using the Percoll gradient method. Cells were cultured with anti-CD3/28 in the presence/absence of DF for 3 to 5 days. Cells were stained and analyzed by flow cytometry. Cytokines were measured by ELISA in cell supernatants. For in vivo experiments, EAE was induced by myelin oligodendrocyte glycoprotein35-55 and mice were treated with oral DF or vehicle daily.RESULTS:
DF acts directly on CD4+ T cells and suppresses GM-CSF-producing Th1 not Th17 or single GM-CSF+ T cells in EAE. In addition, GM-CSF suppression depends on the IFN-γ pathway. We also show that DF specifically suppresses Th1 and GM-CSF-producing Th1 cells in PBMCs from healthy donors.CONCLUSIONS:
We suggest that DF exclusively suppresses GM-CSF-producing Th1 cells in both animal and human CD4+ T cells through an IFN-γ-dependent pathway. These findings indicate that DF has a better therapeutic effect on patients with Th1-dominant immunophenotype. However, future longitudinal study to validate this finding in MS is needed.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Fator Estimulador de Colônias de Macrófagos
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Interferon gama
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Células Th1
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Encefalomielite Autoimune Experimental
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Fumarato de Dimetilo
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Granulócitos
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Fatores Imunológicos
Tipo de estudo:
Observational_studies
Limite:
Adult
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Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article