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http://hdl.handle.net/1942/21732
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DC Field | Value | Language |
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dc.contributor.author | THEWISSEN, Kristof | - |
dc.contributor.author | BROUX, Bieke | - |
dc.contributor.author | HENDRIKS, Jerome | - |
dc.contributor.author | Vanhees, Mandy | - |
dc.contributor.author | STINISSEN, Piet | - |
dc.contributor.author | SLAETS, Leen | - |
dc.contributor.author | HELLINGS, Niels | - |
dc.date.accessioned | 2016-07-13T13:18:32Z | - |
dc.date.available | 2016-07-13T13:18:32Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Cell transplantation, 25 (6), p. 1207-1218 | - |
dc.identifier.issn | 0963-6897 | - |
dc.identifier.uri | http://hdl.handle.net/1942/21732 | - |
dc.description.abstract | The aim of this study is to examine whether the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), can generate dendritic cells (DCs) with a stable tolerogenic phenotype to counteract autoimmune responses in an animal model of multiple sclerosis. We investigated if the tolerogenic potency of DCs could be increased by continuous treatment during in vitro differentiation toward DCs compared to standard 24-h in vitro treatment of already terminally differentiated DCs. We show that in vitro treatment with SAHA reduces the generation of new CD11c(+) DCs out of mouse bone marrow. SAHA-generated DCs show reduced antigen-presenting function as evidenced by a reduction in myelin endocytosis, a decreased MHC II expression, and a failure to upregulate costimulatory molecules upon LPS challenge. In addition, SAHA-generated DCs display a reduction in proinflammatory cytokines and molecules involved in apoptosis induction, inflammatory migration, and TLR signaling, and they are less immunostimulatory compared to untreated DCs. We demonstrated that the underlying mechanism involves a diminished STAT1 phosphorylation and was independent of STAT6 activation. Although in vitro results were promising, SAHA-generated DCs were not able to alleviate the development of experimental autoimmune encephalomyelitis in mice. In vitro washout experiments demonstrated that the tolerogenic phenotype of SAHA-treated DCs is reversible. Taken together, while SAHA potently boosts tolerogenic properties in DCs during the differentiation process in vitro, SAHA-generated DCs were unable to reduce autoimmunity in vivo. Our results imply that caution needs to be taken when developing DC-based therapies to induce tolerance in the context of autoimmune disease. | - |
dc.description.sponsorship | This work was supported by grant No. G.0168.09 of the Fund for Scientific Research-Flanders, Belgium (FWO-Vlaanderen). Further support was provided through the Flemish Institute for Science and Technology (IWT). The authors declare no conflicts of interest. | - |
dc.language.iso | en | - |
dc.publisher | COGNIZANT COMMUNICATION CORP | - |
dc.rights | Copyright © 2016 Cognizant, LLC. | - |
dc.subject.other | Dendritic cells (DCs); Multiple sclerosis; Histone deacetylase inhibitor; Anti-inflammatory; Tolerance | - |
dc.subject.other | Dendritic cells (DCs); multiple sclerosis; histone deacetylase inhibitor; anti-inflammatory; tolerance | - |
dc.title | Tolerogenic Dendritic Cells Generated by In Vitro Treatment With SAHA Are Not Stable In Vivo | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 1218 | - |
dc.identifier.issue | 6 | - |
dc.identifier.spage | 1207 | - |
dc.identifier.volume | 25 | - |
local.format.pages | 12 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | [Thewissen, Kristof; Broux, Bieke; Hendriks, Jerome J. A.; Stinissen, Piet; Slaets, Helena; Hellings, Niels] Hasselt Univ, Biomed Res Inst, Diepenbeek, Belgium. [Thewissen, Kristof; Broux, Bieke; Hendriks, Jerome J. A.; Stinissen, Piet; Slaets, Helena; Hellings, Niels] Transnat Univ Limburg, Sch Life Sci, Diepenbeek, Belgium. [Vanhees, Mandy] Univ Ghent, Dept Clin Chem Microbiol & Immunol, B-9000 Ghent, Belgium. | - |
local.publisher.place | PUTNAM VALLEY | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.3727/096368915X690305 | - |
dc.identifier.isi | 000377847700015 | - |
item.validation | ecoom 2017 | - |
item.contributor | THEWISSEN, Kristof | - |
item.contributor | BROUX, Bieke | - |
item.contributor | HENDRIKS, Jerome | - |
item.contributor | Vanhees, Mandy | - |
item.contributor | STINISSEN, Piet | - |
item.contributor | SLAETS, Leen | - |
item.contributor | HELLINGS, Niels | - |
item.accessRights | Restricted Access | - |
item.fullcitation | THEWISSEN, Kristof; BROUX, Bieke; HENDRIKS, Jerome; Vanhees, Mandy; STINISSEN, Piet; SLAETS, Leen & HELLINGS, Niels (2016) Tolerogenic Dendritic Cells Generated by In Vitro Treatment With SAHA Are Not Stable In Vivo. In: Cell transplantation, 25 (6), p. 1207-1218. | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 0963-6897 | - |
crisitem.journal.eissn | 1555-3892 | - |
Appears in Collections: | Research publications |
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s15.pdf Restricted Access | Published version | 813.42 kB | Adobe PDF | View/Open Request a copy |
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