title: Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193, Bellaterra (Cerdanyola del Vallès), Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Mansilla
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.
authors.forename: Raian
authors.initials: R
authors.lastname: Contreras-Cardone
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193, Bellaterra (Cerdanyola del Vallès), Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Navarro-Barriuso
authors.affiliation: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Antwerp University Hospital, Faculty of Medicine and Health Sciences, University of Antwerp, 2610, Wilrijk, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
authors.affiliation: Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Antwerp University Hospital, Faculty of Medicine and Health Sciences, University of Antwerp, 2610, Wilrijk, Belgium.
authors.forename: Zwi
authors.initials: Z
authors.lastname: Berneman
authors.affiliation: Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramo-Tello
authors.affiliation: Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain. emmartinez.germanstrias@gencat.cat.|Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193, Bellaterra (Cerdanyola del Vallès), Spain. emmartinez.germanstrias@gencat.cat.
authors.forename: Eva María
authors.initials: EM
authors.lastname: Martínez-Cáceres
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000627:therapeutic use*; D017690:Cell Transplantation / Q000379:methods; D002762:Cholecalciferol / Q000627:therapeutic use*; D015925:Cryopreservation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology* / Q000637:transplantation*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011134:Polysaccharides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001324:Autoantigens; D016207:Cytokines; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011134:Polysaccharides; C445081:myelin oligodendrocyte glycoprotein (35-55); D002762:Cholecalciferol
keywords: Breg; EAE; Multiple sclerosis; NK cells; NKT cells; Tolerogenic dendritic cells; Treg