Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients
Mansilla Lopez, Maria Jose (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Contreras-Cardone, Raian (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Navarro-Barriuso, Juan (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cools, Nathalie (University of Antwerp. Vaccine & Infectious Disease Institute)
Berneman, Zwi (University of Antwerp. Vaccine & Infectious Disease Institute)
Ramo-Tello, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez Cáceres, Eva María (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia

Date:	2016
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 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.
Grants:	Ministerio de Economía y Competitividad ISCIII/PI11/02416
Note:	Altres ajuts: Cost Action BM1305
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Breg ; EAE ; Multiple sclerosis ; NK cells ; NKT cells ; Tolerogenic dendritic cells ; Treg
Published in:	Journal of neuroinflammation, Vol. 13, No. 113 (May 2016) , ISSN 1742-2094

DOI: 10.1186/s12974-016-0584-9
PMID: 27207486

11 p, 1.5 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles