Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients

Autologous antigen-specific therapies based on tolerogenic dendritic cells (tolDC) offer the possibility to treat autoimmune diseases by restoring homeostasis and targeting specifically autoreactive responses. Here, we explore the hypothesis that systemic inflammation occurring in autoimmune diseases, such as multiple sclerosis (MS), can generate a disease-specific environment able to alter the functionality of tolDC. In this context in fact, a combined therapy of tolDC with an immunomodulatory treatment could potentiate the beneficial effect of this antigen-specific cell therapy. For this purpose, we analyzed the efficacy of a combined therapy based on the use of vitamin D3 (VitD3)-tolDC plus interferon beta (IFN-beta) in MS. VitD3-tolDC were generated from healthy donors and MS patients and co-cultured with allogeneic peripheral blood mononuclear cells, in the presence or absence of IFN-beta. In vitro, VitD3-tolDC treatment reduced the percentage of activated T cells and allogeneic proliferation, whereas VitD3-tolDC+IFN-beta treatment enhanced the suppressive ability of VitD3-tolDC and, additionally, induced a shift towards a Th2 profile. To determine the clinical benefit of the combined therapy, C57BL/6-experimental autoimmune encephalomyelitis (EAE)-induced mice were treated with antigen-specific VitD3-tolDC and/or IFN-beta. Treatment of EAE mice with combined therapy ameliorated the disease course compared to each monotherapy. These results suggest that a combined therapy based on antigen-specific VitD3-tolDC and IFN-beta may represent a promising strategy for MS patients.

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Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510379611 ◽

2010 ◽

Vol 16 (12) ◽

pp. 1513-1516 ◽

Cited By ~ 29

Author(s):

Halina Bartosik-Psujek ◽

Jacek Tabarkiewicz ◽

Krystyna Pocinska ◽

Zbigniew Stelmasiak ◽

Jacek Rolinski

Keyword(s):

Multiple Sclerosis ◽

Dendritic Cells ◽

Vitamin D3 ◽

Cell Sorting ◽

Immunomodulatory Effects ◽

Relapsing Remitting ◽

Beneficial Action ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

In order to evaluate the effects of vitamin D3 on monocyte-derived dendritic cells (DCs) of relapsing—remitting multiple sclerosis patients, DCs differentiation and maturation were evaluated in vitro based on surface phenotypic changes. The expression of CD14, CD83, CD1a, CD80, CD86, CD206 and C209 was analysed by fluorescence-activated cell sorting. The results reveal that vitamin D3 inhibits both the differentiation and maturation of DCs. Moreover, inhibits the secretion of IL 23/12p40 and increases the secretion of CCL2. The data suggest that one of the mechanisms of the beneficial action of vitamin D3 in multiple sclerosis may be associated with its influence on DCs.

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Assessment of biochemical determinants in Multiple Sclerosis patients following the oral administration of β-D-Mannuronic acid [M2000]

Current Drug Discovery Technologies ◽

10.2174/1570163817999200918104333 ◽

2020 ◽

Vol 17 ◽

Author(s):

Mohamad Reza Nikouei Moghaddam ◽

Monireh Movahedi ◽

Maryam Bananej ◽

Soheil Najafi ◽

Nahid Beladi Moghadam ◽

...

Keyword(s):

Multiple Sclerosis ◽

Uric Acid ◽

Vitamin D3 ◽

Chronic Inflammatory Disease ◽

Toxic Effects ◽

Control Group ◽

Therapeutic Effects ◽

Mannuronic Acid ◽

Anti Inflammatory ◽

Multiple Sclerosis Patients

Background: Multiple sclerosis is an autoimmune chronic inflammatory disease of the central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression completely, and have some unwanted side effects too. The immunomodulatory and anti-inflammatory effects of the β-D-Mannuronic acid [M2000] have been proven in several surveys, and the present research was designed to determine its toxicity and therapeutic effects in MS patients. Methods: This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate the therapeutic and possible toxic effects of this drug after this period. Results: Non- toxic effects through the study of Urea, Creatinine, GGT, and non-significant changes in Uric acid and AntiPhospholipids levels, besides a significant rise in Vitamin, D3 levels in the M2000 treated cases were found. Conclusions: Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity when administered orally and also has some therapeutic effects in MS patients.

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Therapeutic Effect of Vitamin D3 in Multiple Sclerosis Patients

Immunological Investigations ◽

10.3109/08820139.2011.573041 ◽

2011 ◽

Vol 40 (6) ◽

pp. 627-639 ◽

Cited By ~ 83

Author(s):

Ghasem Mosayebi ◽

Ali Ghazavi ◽

Keyvan Ghasami ◽

Yahya Jand ◽

Parviz Kokhaei

Keyword(s):

Multiple Sclerosis ◽

Therapeutic Effect ◽

Vitamin D3 ◽

Multiple Sclerosis Patients

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Ultraviolet B Radiation Therapy Versus Vitamin D3 Supplementation: Effects on Cognitive Functions and Fatigue in Egyptian Relapsing Remitting Multiple Sclerosis Patients

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2019.11.080 ◽

2020 ◽

Vol 37 ◽

pp. 101605

Author(s):

Alaa Elmazny ◽

Asmaa Ibrahim ◽

Hatem Shehata ◽

Nevin Shalaby ◽

Eman Magdy ◽

...

Keyword(s):

Multiple Sclerosis ◽

Radiation Therapy ◽

Vitamin D3 ◽

Cognitive Functions ◽

Ultraviolet B ◽

Ultraviolet B Radiation ◽

Relapsing Remitting ◽

Vitamin D3 Supplementation ◽

Multiple Sclerosis Patients ◽

Relapsing Remitting Multiple Sclerosis

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Impact of type-I-interferon on monocyte subsets and their differentiation to dendritic cells An in vivo and ex vivo study in multiple sclerosis patients treated with interferon-beta

Journal of Neuroimmunology ◽

10.1016/j.neuroim.2003.10.037 ◽

2003 ◽

Author(s):

F Bergh

Keyword(s):

Multiple Sclerosis ◽

Dendritic Cells ◽

Interferon Beta ◽

Type I Interferon ◽

Ex Vivo ◽

Type I ◽

Monocyte Subsets ◽

Multiple Sclerosis Patients ◽

Ex Vivo Study

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FTY720 (fingolimod) treatment tips the balance towards less immunogenic antigen-presenting cells in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515574895 ◽

2015 ◽

Vol 21 (14) ◽

pp. 1811-1822 ◽

Cited By ~ 20

Author(s):

Felix Luessi ◽

Stefan Kraus ◽

Bettina Trinschek ◽

Steffen Lerch ◽

Robert Ploen ◽

...

Keyword(s):

Multiple Sclerosis ◽

Dendritic Cells ◽

Healthy Subjects ◽

Ex Vivo ◽

Antigen Presenting Cells ◽

Direct Effects ◽

Quantitative Analyses ◽

Ifn Γ ◽

Multiple Sclerosis Patients ◽

Antigen Presenting

Objective: We aimed to clarify whether fingolimod has direct effects on antigen-presenting cells in multiple sclerosis patients. Methods: Frequency and phenotype of directly ex vivo dendritic cells and monocytes were analyzed in 43 individuals, including fingolimod-treated and untreated multiple sclerosis patients as well as healthy subjects. These cells were further stimulated with lipopolysaccharide to determine functional effects of fingolimod treatment. Results: Absolute numbers of CD1c+ dendritic cells and monocytes were not significantly reduced in fingolimod-treated patients indicating that fingolimod did not block the migration of antigen-presenting cells to peripheral blood. CD86 was upregulated on CD1c+ dendritic cells and thus their activation was not impaired under fingolimod treatment. Quantitative analyses of gene transcription in cells and protein content in supernatants from ex vivo CD1c+ dendritic cells and monocytes, however, showed lower secretion of TNFα, IL1-β and IL-6 upon lipopolysaccharide-stimulation. These results could be matched with CD4+MOG-specific transgenic T cells exhibiting reduced levels of TNFα and IFN-γ but not IL-4 upon stimulation with murine dendritic cells loaded with MOG, when treated with fingolimod. Conclusions: Our data indicate that fingolimod – apart from trapping lymphocytes in lymph nodes – exerts its disease-modulating activity by rebalancing the immune tolerance networks by modulation of antigen-presenting cells.

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