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.artnumber","e0143954"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Montes-Cobos, Elena"],["dc.contributor.author","Li, Xiao"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Sasse, André"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Didié, Michael"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Fassnacht, Martin"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2018-11-07T09:48:47Z"],["dc.date.available","2018-11-07T09:48:47Z"],["dc.date.issued","2015"],["dc.description.abstract","Mineralocorticoid receptor (MR) inactivation in mice results in early postnatal lethality. Therefore we generated mice in which MR expression can be silenced during adulthood by administration of doxycycline (Dox). Using a lentiviral approach, we obtained two lines of transgenic mice harboring a construct that allows for regulatable MR inactivation by RNAi and concomitant expression of eGFP. MR mRNA levels in heart and kidney of inducible MR knock-down mice were unaltered in the absence of Dox, confirming the tightness of the system. In contrast, two weeks after Dox administration MR expression was significantly diminished in a variety of tissues. In the kidney, this resulted in lower mRNA levels of selected target genes, which was accompanied by strongly increased serum aldosterone and plasma renin levels as well as by elevated sodium excretion. In the healthy heart, gene expression and the amount of collagen were unchanged despite MR levels being significantly reduced. After transverse aortic constriction, however, cardiac hypertrophy and progressive heart failure were attenuated by MR silencing, fibrosis was unaffected and mRNA levels of a subset of genes reduced. Taken together, we believe that this mouse model is a useful tool to investigate the role of the MR in pathophysiological processes."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.1371/journal.pone.0143954"],["dc.identifier.isi","000365865300124"],["dc.identifier.pmid","26605921"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12615"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35378"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/129"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","1932-6203"],["dc.relation.workinggroup","RG Dressel"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Inducible Knock-Down of the Mineralocorticoid Receptor in Mice Disturbs Regulation of the Renin-Angiotensin-Aldosterone System and Attenuates Heart Failure Induced by Pressure Overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]