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Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients [Methylation_array]

ABSTRACT: Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients [Methylation_array]

PROVIDER: PRJNA1112366 | ENA |

REPOSITORIES: ENA

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Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients

Project description:Multiple Sclerosis (MS) is a chronic disease characterised by dysregulated self-reactive immune responses damaging neurons’ myelin sheath, causing disability. The primary therapeutic option, immunosuppressants, inhibit pathogenic anti-myelin responses but depresses the entire immune system. Antigen-specific autologous tolerogenic dendritic cell (tolDC) therapies offer an approach to restore tolerance to auto-antigens without causing generalised immunosuppression. However, immune dysregulation in MS could impact the phenotype and functionality of the starting material for cell therapy. In this study, we defined the immune signature of CD14+ monocytes, mature dendritic cells (mDCs) and Vitamin D3 tolDCs (VitD3-tolDCs) isolated from MS patients and healthy donors (HD). By using a multi-omic approach, we identified a shift in these cell types toward a proinflammatory profile dominated by alterations in the AhR pathway and increased NFkB signalling. Moreover, tolDCs isolated from MS patients showed reduced tolerogenic properties compared to those from HD, which were fully restored through AhR agonism and NFkB downregulation through in vivo or in vitro supplementation with Dimethyl Fumarate (DMF). Remarkably, a combined therapy of DMF and VitD3-tolDC was more efficient to reduce the clinical score of experimental autoimmune encephalomyelitis mice than monotherapies. In summary, we demonstrate that DMF restores the functionality of VitD3-tolDCs derived from MS patients. Moreover, a combined therapy with DMF and VitD3-tolDCs could offer enhanced therapeutic potential in treating MS.

2024-12-13 | GSE267576 | GEO

Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients [Methylation_array]

2024-12-13 | GSE267660 | GEO

Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients

Project description:Dimethyl Fumarate Restores Functional Vitamin-D3 Tolerogenic Dendritic Cells differentiated from Multiple Sclerosis Patients

| PRJNA1111870 | ENA

Expression data of renal cancer cell treated with Oncolytic virus VSVd51 and Fumaric acid esters such as Dimethyl fumarate

Project description:We propose a strategy to boost the therapeutic efficacy of Oncolytic therapy by combining it with fumaric acid ester such as Dimethyl fumarate (DMF) The mechanism of action was examined by microarray analysis using the Affymetrix Human PrimeView Array.

2018-07-30 | GSE97328 | GEO

Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells

Project description:Primary human and mouse T cells were treated with the multiple sclerosis drug dimethyl fumarate (DMF) or its in vivo metabolite monomethyl fumarate (MMF). Cysteines sensitive to DMF or MMF were identified using iodoacetamide alkyne enrichment.

2016-08-31 | MSV000080111 | MassIVE

Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia

Project description:Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood-brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood and there is a need to characterize if DMF or its bioactive metabolite monomethyl fumarate (MMF) exert neuroprotective properties. The combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection. The aim of this study was to compare the effects of DMF, MMF and CBD on neuroprotective and immunomodulatory pathways in neurons and microglia in vitro. We found that DMF and CBD, but not MMF, activated the Nrf2 antioxidant pathway in neurons. Similarly, only DMF and CBD, but not MMF, prevented the LPS-induced activation of the inflammatory pathway NF-kB in microglia. However, the 3 drugs inhibited the production of nitric oxide in microglia and protected neurons against apoptosis. Transcriptomically, DMF, MMF and CBD exhibited differential effects on these pathways, with DMF achieving the most pronounced changes. Our results show that DMF and MMF, despite being structurally related, present differences in their mechanisms of action that could be relevant for the achievement of neuroprotection in MS patients and the potential of CBD as an adjuvant therapy in neuroprotection.

2024-09-30 | GSE274435 | GEO

Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia

Project description:Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia

| PRJNA1146415 | ENA

Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia [Mouse]

2024-09-30 | GSE274859 | GEO

Microarray of tolerogenic dendritic cells differentiated in the presence of vitamin D3, dexamethasone or rapamycin

Project description:The comparative analysis of the transcriptome of tolerogenic dendritic cells (tolDC) differentiated using different stimulus (either vitamin D3, dexamethasone or rapamycin) would allow to evidence potential common genes and pathways that could explain their potency as tolerance-inducing cells.

2018-07-31 | E-MTAB-6937 | biostudies-arrayexpress

Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia [Mouse]

Project description:Differential neuroprotective and anti-inflammatory effects of dimethyl fumarate, monomethyl fumarate and cannabidiol in neurons and microglia [Mouse]

| PRJNA1148203 | ENA

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