Cryopreserved vitamin D<inf>3</inf>-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients

María José Mansilla, Raian Contreras-Cardone, Juan Navarro-Barriuso, Nathalie Cools, Zwi Berneman, Cristina Ramo-Tello, Eva María Martínez-Cáceres

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

© 2016 Mansilla et al. 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 D3 (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.
Original languageEnglish
Article number113
JournalJournal of Neuroinflammation
Volume13
Issue number1
DOIs
Publication statusPublished - 20 May 2016

Keywords

  • Breg
  • EAE
  • Multiple sclerosis
  • NK cells
  • NKT cells
  • Tolerogenic dendritic cells
  • Treg

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