Montes-Cobos, Elena

[["dc.bibliographiccitation.firstpage","646"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","655"],["dc.bibliographiccitation.volume","235"],["dc.contributor.author","Theiss-Suennemann, Jennifer"],["dc.contributor.author","Joerss, Katharina"],["dc.contributor.author","Messmann, Joanna J."],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Montes-Cobos, Elena"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Wolff, Hendrik Andreas"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Groene, Hermann-Josef"],["dc.contributor.author","Strauss, Gudrun"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:00:41Z"],["dc.date.available","2018-11-07T10:00:41Z"],["dc.date.issued","2015"],["dc.description.abstract","Glucocorticoids (GCs) are released from the adrenal gland during inflammation and help to keep immune responses at bay. Owing to their potent anti-inflammatory activity, GCs also play a key role in controlling acute graft-versus-host disease (aGvHD). Here we demonstrate that mice lacking the glucocorticoid receptor (GR) in T cells develop fulminant disease after allogeneic bone marrow transplantation. In a fully MHC-mismatched model, transfer of GR-deficient T cells resulted in severe aGvHD symptoms and strongly decreased survival times. Histopathological features were aggravated and infiltration of CD8(+) T cells into the jejunum was increased when the GR was not expressed. Furthermore, serum levels of IL-2, IFN, and IL-17 were elevated and the cytotoxicity of CD8(+) T cells was enhanced after transfer of GR-deficient T cells. Short-term treatment with dexamethasone reduced cytokine secretion but neither impacted disease severity nor the CTLs' cytolytic capacity. Importantly, in an aGvHD model in which disease development exclusively depends on the presence of CD8(+) T cells in the transplant, transfer of GR-deficient T cells aggravated clinical symptoms and reduced survival times as well. Taken together, our findings highlight that suppression of CD8(+) T-cell function is a crucial mechanism in the control of aGvHD by endogenous GCs. Copyright (c) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd."],["dc.identifier.doi","10.1002/path.4475"],["dc.identifier.isi","000349677700011"],["dc.identifier.pmid","25358639"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37861"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1096-9896"],["dc.relation.issn","0022-3417"],["dc.title","Glucocorticoids attenuate acute graft-versus-host disease by suppressing the cytotoxic capacity of CD8(+) T cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","157"],["dc.bibliographiccitation.journal","Journal of Controlled Release"],["dc.bibliographiccitation.lastpage","169"],["dc.bibliographiccitation.volume","245"],["dc.contributor.author","Montes-Cobos, Elena"],["dc.contributor.author","Ring, Sarah"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Heck, Joachim G."],["dc.contributor.author","Strauss, Judith"],["dc.contributor.author","Schwaninger, Markus"],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Feldmann, Claus"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:28:25Z"],["dc.date.available","2018-11-07T10:28:25Z"],["dc.date.issued","2017"],["dc.description.abstract","Glucocorticoids (GC) are widely used to treat acute relapses in multiple sclerosis (MS) patients, but their application is accompanied by side effects due to their broad spectrum of action. Here, we report on the therapeutic option to apply GC via inorganic-organic hybrid nanoparticles (IOH-NP) with the composition [ZrO](2+)[(BMP)(0.9)(FMN)(0.1)](2-) (designated BMP-NP with BMP: betamethasone phosphate; FMN: flavinmononucleotide). We found that these BMP-NP have an increased cell type-specificity compared to free GC while retaining full therapeutic efficacy in a mouse model of MS. BMP-NP were preferentially taken up by phagocytic cells and modulated macrophages in vivo more efficiently than T cells. When GC were applied in the form of BMP-NP, treatment of neuroinflammatory disease in mice exclusively depended on the control of macrophage function whereas effects on T cells and brain endothelial cells were dispensable for therapeutic efficacy. Importantly, BMP-NP were not only active in mice but also showed strong activity towards monocytes isolated from healthy human volunteers. We conclude that application of GC via IOH-NP has the potential to improve MS therapy in the future. (C) 2016 Elsevier B.V. All rights reserved."],["dc.description.sponsorship","German Research Foundation (DFG) [RE 1631/15-1, LU 634/9-1]"],["dc.identifier.doi","10.1016/j.jconrel.2016.12.003"],["dc.identifier.isi","000396474500015"],["dc.identifier.pmid","27919626"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43416"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1873-4995"],["dc.relation.issn","0168-3659"],["dc.title","Targeted delivery of glucocorticoids to macrophages in a mouse model of multiple sclerosis using inorganic-organic hybrid nanoparticles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]