Title
Cryopreserved vitamin D-3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patientsCryopreserved vitamin D-3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Research group
Vaccine & Infectious Disease Institute (VAXINFECTIO)
Publication type
article
Publication
London,
Subject
Human medicine
Source (journal)
Journal of neuroinflammation. - London
Volume/pages
13(2016), 11 p.
ISSN
1742-2094
1742-2094
Article Reference
113
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Background: Tolerogenic dendritic cells (tolDC) have been postulated as a potent immunoregulatory therapy for autoimmune diseases such as multiple sclerosis (MS). In a previous study, we demonstrated that the administration of antigen-specific vitamin D-3 (vitD3) tolDC in mice showing clinical signs of experimental autoimmune encephalomyelitis (EAE; the animal model of MS) resulted in abrogation of disease progression. With the purpose to translate this beneficial therapy to the clinics, we have investigated the effectivity of vitD3-frozen antigen-specific tolDC pulsed with myelin oligodendrocyte glycoprotein 40-55 peptide (f-tolDC-MOG) since it would reduce the cost, functional variability and number of leukapheresis to perform to the patients. Methods: Mice showing EAE clinical signs were treated with repetitive doses of f-tolDC-MOG. Tolerogenic mechanisms induced by the therapy were analysed by flow cytometry and T cell proliferation assays. Results: Treatment with f-tolDC-MOG was effective in ameliorating clinical signs of mice with EAE, inhibiting antigen-specific reactivity and inducing Treg. In addition, the long-term treatment was well tolerated and leading to a prolonged maintenance of tolerogenicity mediated by induction of Breg, reduction of NK cells and activation of immunoregulatory NKT cells. Conclusions: The outcomes of this study show that the use of antigen-specific f-tolDC promotes multiple and potent tolerogenic mechanisms. Moreover, these cells can be kept frozen maintaining their tolerogenic properties, which is a relevant step for their translation to the clinic. Altogether, vitD3 f-tolDC-MOG is a potential strategy to arrest the autoimmune destruction in MS patients.
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/449775/134216.pdf
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