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dc.contributor.authorLynch, Kevin
dc.contributor.authorTreacy, Oliver
dc.contributor.authorGerlach, Jared Q.
dc.contributor.authorAnnuk, Heidi
dc.contributor.authorLohan, Paul
dc.contributor.authorCabral, Joana
dc.contributor.authorJoshi, Lokesh
dc.contributor.authorRyan, Aideen E.
dc.contributor.authorRitter, Thomas
dc.date.accessioned2017-11-08T10:06:22Z
dc.date.available2017-11-08T10:06:22Z
dc.date.issued2017-10-30
dc.identifier.citationLynch, Kevin, Treacy, Oliver, Gerlach, Jared Q., Annuk, Heidi, Lohan, Paul, Cabral, Joana, Joshi, Lokesh, Ryan, Aideen E., Ritter, Thomas. (2017). Regulating Immunogenicity and Tolerogenicity of Bone Marrow-Derived Dendritic Cells through Modulation of Cell Surface Glycosylation by Dexamethasone Treatment. Frontiers in Immunology, 8(1427). doi: 10.3389/fimmu.2017.01427en_IE
dc.identifier.issn1664-3224
dc.identifier.urihttp://hdl.handle.net/10379/6955
dc.description.abstractDendritic cellular therapies and dendritic cell vaccines show promise for the treatment of autoimmune diseases, the prolongation of graft survival in transplantation, and in educating the immune system to fight cancers. Cell surface glycosylation plays a crucial role in the cell-cell interaction, uptake of antigens, migration, and homing of DCs. Glycosylation is known to change with environment and the functional state of DCs. Tolerogenic DCs (tDCs) are commonly generated using corticosteroids including dexamethasone, however, to date, little is known on how corticosteroid treatment alters glycosylation and what functional consequences this may have. Here, we present a comprehensive profile of rat bone marrow-derived dendritic cells, examining their cell surface glycosylation profile before and after Dexa treatment as resolved by both lectin microarrays and lectin-coupled flow cytometry. We further examine the functional consequences of altering cell surface glycosylation on immunogenicity and tolerogenicity of DCs. Dexa treatment of rat DCs leads to profoundly reduced expression of markers of immunogenicity (MHC I/II, CD80, CD86) and pro-inflammatory molecules (IL-6, IL-12p40, inducible nitric oxide synthase) indicating a tolerogenic phenotype. Moreover, by comprehensive lectin microarray profiling and flow cytometry analysis, we show that sialic acid (Sia) is significantly upregulated on tDCs after Dexa treatment, and that this may play a vital role in the therapeutic attributes of these cells. Interestingly, removal of Sia by neuraminidase treatment increases the immunogenicity of immature DCs and also leads to increased expression of pro-inflammatory cytokines while tDCs are moderately protected from this increase in immunogenicity. These findings may have important implications in strategies aimed at increasing tolerogenicity where it is advantageous to reduce immune activation over prolonged periods. These findings are also relevant in therapeutic strategies aimed at increasing the immunogenicity of cells, for example, in the context of tumor specific immunotherapies.en_IE
dc.description.sponsorshipThis work is supported by Science Foundation Ireland (12/TIDA/B2370 and 12/IA/1624) and European Cooperation in Science and Technology (COST) for the AFACTT project (Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies; BM1305).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherFrontiers Mediaen_IE
dc.relation.ispartofFrontiers In Immunologyen
dc.subjecttolerogenic dendritic cellsen_IE
dc.subjectglycosylationen_IE
dc.subjectdexamethasoneen_IE
dc.subjectimmunogenicityen_IE
dc.subjecttolerogenicityen_IE
dc.subjectsialic aciden_IE
dc.subjectautoimmunityen_IE
dc.subjectcell therapyen_IE
dc.subjectSELECTIN GLYCOPROTEIN LIGAND-1en_IE
dc.subjectT-CELLSen_IE
dc.subjectIMMUNE-SYSTEMen_IE
dc.subjectCALCINEURIN INHIBITORSen_IE
dc.subjectORGAN-TRANSPLANTATIONen_IE
dc.subjectSIALIC ACIDSen_IE
dc.subjectP-SELECTINen_IE
dc.subjectDIFFERENTIATIONen_IE
dc.subjectMATURATIONen_IE
dc.subjectINDUCTIONen_IE
dc.titleRegulating immunogenicity and tolerogenicity of bone marrow-derived dendritic cells through modulation of cell surface glycosylation by dexamethasone treatmenten_IE
dc.typeArticleen_IE
dc.date.updated2017-11-08T09:34:14Z
dc.identifier.doi10.3389/fimmu.2017.01427
dc.local.publishedsourcehttps://doi.org/10.3389/fimmu.2017.01427en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funder|~|1267872|~|1267883|~|
dc.internal.rssid13418937
dc.local.contactThomas Ritter, School Of Medicine, Regenerative Medicine Institute, Biosciences, Dangan. 5329 Email: thomas.ritter@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
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