Immunomodulatory Effects of 1,25-Dihydroxyvitamin D on Dendritic Cells Promote Induction of T Cell Hyporesponsiveness to Myelin-Derived Antigens
Lee, Wai-Ping (Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium)
Willekens, Barbara (University Hospital Antwerp (Bèlgica))
Cras, Patrick (Department of Neurology, Born Bunge Institute, Translational Neurosciences, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium)
Goossens, Herman (Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium)
Martínez Cáceres, Eva María (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Berneman, Zwi (University Hospital Antwerp (Bèlgica))
Cools, Nathalie (Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium)

Fecha:	2016
Resumen:	While emerging evidence indicates that dendritic cells (DC) play a central role in the pathogenesis of multiple sclerosis (MS), their modulation with immunoregulatory agents provides prospect as disease-modifying therapy. Our observations reveal that 1,25-dihydroxyvitamin D (1,25(OH)D) treatment of monocyte-derived DC results in a semimature phenotype and anti-inflammatory cytokine profile as compared to conventional DC, in both healthy controls and MS patients. Importantly, 1,25(OH)D-treated DC induce T cell hyporesponsiveness, as demonstrated in an allogeneic mixed leukocyte reaction. Next, following a freeze-thaw cycle, 1,25(OH)D-treated immature DC could be recovered with a 78% yield and 75% viability. Cryopreservation did not affect the expression of membrane markers by 1,25(OH)D-treated DC nor their capacity to induce T cell hyporesponsiveness. In addition, the T cell hyporesponsiveness induced by 1,25(OH)D-treated DC is antigen-specific and robust since T cells retain their capacity to respond to an unrelated antigen and do not reactivate upon rechallenge with fully mature conventional DC, respectively. These observations underline the clinical potential of tolerogenic DC (tolDC) to correct the immunological imbalance in MS. Furthermore, the feasibility to cryopreserve highly potent tolDC will, ultimately, contribute to the large-scale production and the widely applicable use of tolDC.
Ayudas:	Instituto de Salud Carlos III PI14-01175
Nota:	Altres ajuts: This work was supported by positive discussion through the A FACTT network (Cost Action BM1305: http://www.afactt.eu/). COST is supported by the EU Framework Programme Horizon 2020. Further support was provided by Grant no. G.0168.09 of the Fund for Scientific Research-Flanders, Belgium (FWO-Vlaanderen), by an applied biomedical research project of the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-TBM 140191), by the grants of the University of Antwerp through the Special Research Fund (BOF), a BOF-GOA grant (ID PS 28313), Medical Legacy Fund, the Methusalem funding programme, the Belgian Hercules Foundation, by grants of the Charcot Foundation, Belgium, and of the "Belgische Stichting Roeping," Belgium, ∑. The authors also thank the NIH AIDS Research and Reference Reagent Programme for providing the CMV pp65 peptide pool. WaiPing Lee held a Ph.D. fellowship of the Flemish Institute for Science and Technology (IWT).
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Journal of Immunology Research, Vol. 2016 (september 2016) , ISSN 2314-7156

DOI: 10.1155/2016/5392623
PMID: 27703987

16 p, 1.7 MB

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