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1,25-Dihydroxyvitamin D3 promotes tolerogenic dendritic cells with functional migratory properties in NOD mice

2014-05-01Journal article Restricted access
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dc.contributor.authorFerreira, Gabriela B
dc.contributor.authorGysemans, Conny A
dc.contributor.authorDemengeot, Jocelyne
dc.contributor.authorda Cunha, João Paulo M C M
dc.contributor.authorVanherwegen, An-Sofie
dc.contributor.authorOverbergh, Lut
dc.contributor.authorVan Belle, Tom L
dc.contributor.authorPauwels, Femke
dc.contributor.authorVerstuyf, Annemieke
dc.contributor.authorKorf, Hannelie
dc.contributor.authorMathieu, Chantal
dc.date.accessioned2018-03-05T16:48:01Z
dc.date.available2018-03-05T16:48:01Z
dc.date.issued2014-05-01
dc.descriptionThis deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: http://www.jimmunol.org/content/192/9/4210.long#ack-1pt_PT
dc.descriptionThis publication hasn't any creative commons license associated.pt_PT
dc.description.abstractThe biologically active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is able to promote the generation of tolerogenic mature dendritic cells (mDCs) with an impaired ability to activate autoreactive T cells. These cells could represent a reliable tool for the promotion or restoration of Ag-specific tolerance through vaccination strategies, for example in type 1 diabetes patients. However, successful transfer of 1,25(OH)2D3-treated mDCs (1,25D3-mDCs) depends on the capacity of 1,25(OH)2D3 to imprint a similar tolerogenic profile in cells derived from diabetes-prone donors as from diabetes-resistant donors. In this study, we examined the impact of 1,25(OH)2D3 on the function and phenotype of mDCs originating from healthy (C57BL/6) and diabetes-prone (NOD) mice. We show that 1,25(OH)2D3 is able to imprint a phenotypic tolerogenic profile on DCs derived from both mouse strains. Both NOD- and C57BL/6-derived 1,25D3-mDCs decreased the proliferation and activation of autoreactive T cells in vitro, despite strain differences in the regulation of cytokine/chemokine expression. In addition, 1,25D3-mDCs from diabetes-prone mice expanded CD25(+)Foxp3(+) regulatory T cells and induced intracellular IL-10 production by T cells in vitro. Furthermore, 1,25D3-mDCs exhibited an intact functional migratory capacity in vivo that favors homing to the liver and pancreas of adult NOD mice. More importantly, when cotransferred with activated CD4(+) T cells into NOD.SCID recipients, 1,25D3-mDCs potently dampened the proliferation of autoreactive donor T cells in the pancreatic draining lymph nodes. Altogether, these results argue for the potential of 1,25D3-mDCs to restore Ag-specific immune tolerance and arrest autoimmune disease progression in vivo.pt_PT
dc.description.sponsorshipThis work/publication was supported by grants from the Flemish Research Foundation (Fonds Voor Wetenschappelijk Onderzoek Vlaanderen G.0649.08, G.0734.10, and 1.5.118.13N; postdoctoral fellowships to G.B.F. and H.K.; and a clinical fellowship to C.M.), the Belgium Program on Interuniversity Poles of Attraction initiated by the Belgian State (P6/40), the Katholieke Universiteit Leuven (GOA 2009/010 and GOA 14/010), the Seventh Framework Program of the European Union with Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes, and the Diabetes Fonds Nederland (Diabetes Fonds Nederland Expert Center β Cell Immunoprotection).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citation1,25-Dihydroxyvitamin D3 Promotes Tolerogenic Dendritic Cells with Functional Migratory Properties in NOD Mice Gabriela B. Ferreira, Conny A. Gysemans, Jocelyne Demengeot, João Paulo M. C. M. da Cunha, An-Sofie Vanherwegen, Lut Overbergh, Tom L. Van Belle, Femke Pauwels, Annemieke Verstuyf, Hannelie Korf, Chantal Mathieu The Journal of Immunology May 1, 2014, 192 (9) 4210-4220; DOI: 10.4049/jimmunol.1302350pt_PT
dc.identifier.doi10.4049/jimmunol.1302350pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/848
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Association of Immunologistspt_PT
dc.relation.publisherversionhttp://www.jimmunol.org/content/192/9/4210.longpt_PT
dc.subjectAnimalspt_PT
dc.subjectChemotaxis, Leukocytept_PT
dc.subjectDendritic Cellspt_PT
dc.subjectFlow Cytometrypt_PT
dc.subjectFluorescent Antibody Techniquept_PT
dc.subjectImmune Tolerancept_PT
dc.subjectLymphocyte Activationpt_PT
dc.subjectMicept_PT
dc.subjectMice, Inbred C57BLpt_PT
dc.subjectMice, Inbred NODpt_PT
dc.subjectMice, Transgenicpt_PT
dc.subjectPhenotypept_PT
dc.subjectReal-Time Polymerase Chain Reactionpt_PT
dc.subjectVitamin Dpt_PT
dc.title1,25-Dihydroxyvitamin D3 promotes tolerogenic dendritic cells with functional migratory properties in NOD micept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage4220pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage4210pt_PT
oaire.citation.titleJournal of Immunologypt_PT
oaire.citation.volume192pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT

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