Reichardt, Holger Michael

[["dc.bibliographiccitation.firstpage","2384"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","American Journal of Transplantation"],["dc.bibliographiccitation.lastpage","2394"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Siepert, Anja"],["dc.contributor.author","Ahrlich, S."],["dc.contributor.author","Vogt, K."],["dc.contributor.author","Appelt, C."],["dc.contributor.author","Stanko, K."],["dc.contributor.author","Kühl, Anja A."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Nizze, H."],["dc.contributor.author","Lehmann, M."],["dc.contributor.author","Tiedge, Markus"],["dc.contributor.author","Volk, H.-D."],["dc.contributor.author","Sawitzki, Birgit"],["dc.contributor.author","Reinke, Petra"],["dc.date.accessioned","2018-11-07T09:06:43Z"],["dc.date.available","2018-11-07T09:06:43Z"],["dc.date.issued","2012"],["dc.description.abstract","Recent data suggest that donor-specific memory T cells (Tmem) are an independent risk factor for rejection and poor graft function in patients and a major challenge for immunosuppression minimizing strategies. Many tolerance induction protocols successfully proven in small animal models e.g. costimulatory blockade, T cell depletion failed in patients. Consequently, there is a need for more predictive transplant models to evaluate novel promising strategies, such as adoptive transfer of regulatory T cells (Treg). We established a clinically more relevant, life-supporting rat kidney transplant model using a high responder (DA to LEW) recipients that received donor-specific CD4+/ 8+ GFP+ Tmem before transplantation to achieve similar pre-transplant frequencies of donor-specific Tmem as seen in many patients. T cell depletion alone induced long-term graft survival in naive recipients but could not prevent acute rejection in Tmem+ rats, like in patients. Only if T cell depletion was combined with permanent CNI-treatment, the intragraft inflammation, and acute/chronic allograft rejection could be controlled long-term. Remarkably, combining 10 days CNI treatment and adoptive transfer of Tregs (day 3) but not Treg alone also induced long-term graft survival and an intragraft tolerance profile (e.g. high TOAG-1) in Tmem+ rats. Our model allows evaluation of novel therapies under clinically relevant conditions."],["dc.identifier.doi","10.1111/j.1600-6143.2012.04143.x"],["dc.identifier.isi","000307945000017"],["dc.identifier.pmid","22702307"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25617"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1600-6135"],["dc.title","Permanent CNI Treatment for Prevention of Renal Allograft Rejection in Sensitized Hosts Can Be Replaced by Regulatory 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","359"],["dc.bibliographiccitation.journal","BMC Genomics"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Frijters, Raoul"],["dc.contributor.author","Fleuren, Wilco"],["dc.contributor.author","Toonen, Erik J. M."],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","van der Maaden, Hans"],["dc.contributor.author","van Elsas, Andrea"],["dc.contributor.author","van Lierop, Marie-Jose"],["dc.contributor.author","Dokter, Wim"],["dc.contributor.author","de Vlieg, Jacob"],["dc.contributor.author","Alkema, Wynand"],["dc.date.accessioned","2018-11-07T08:42:18Z"],["dc.date.available","2018-11-07T08:42:18Z"],["dc.date.issued","2010"],["dc.description.abstract","Background: Glucocorticoids (GCs) control expression of a large number of genes via binding to the GC receptor (GR). Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT) and mice that have lost the ability to form GR dimers (GR(dim)). Results: The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GR(dim) mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GR(dim) mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GR(dim) mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions: This study on prednisolone-induced effects in livers of WT and GR(dim) mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs."],["dc.description.sponsorship","Netherlands Bioinformatics Centre (NBIC)"],["dc.identifier.doi","10.1186/1471-2164-11-359"],["dc.identifier.isi","000279868400001"],["dc.identifier.pmid","20525385"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5804"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19668"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2164"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","48"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","61"],["dc.bibliographiccitation.volume","199"],["dc.contributor.author","Klaßen, Carina"],["dc.contributor.author","Karabinskaya, Anna"],["dc.contributor.author","Dejager, Lien"],["dc.contributor.author","Vettorazzi, Sabine"],["dc.contributor.author","Van Moorleghem, Justine"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Meijsing, Sebastiaan H."],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Libert, Claude"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2020-12-10T18:47:42Z"],["dc.date.available","2020-12-10T18:47:42Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.4049/jimmunol.1601691"],["dc.identifier.eissn","1550-6606"],["dc.identifier.issn","0022-1767"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78852"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Wiener klinische Wochenschrift"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Mueller, N."],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T11:12:50Z"],["dc.date.available","2018-11-07T11:12:50Z"],["dc.date.issued","2008"],["dc.format.extent","63"],["dc.identifier.isi","000259367100198"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53752"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.issn","0043-5325"],["dc.title","Repression of T effector cells by glucocorticoids through rapid modulation of the F-actin cytoskeleton by non-genomic mechanisms"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1319"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.lastpage","13"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Montes-Cobos, Elena"],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Li, Xiao"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Reichardt, Holger M."],["dc.contributor.author","Lühder, Fred"],["dc.date.accessioned","2019-07-09T11:44:30Z"],["dc.date.available","2019-07-09T11:44:30Z"],["dc.date.issued","2017"],["dc.description.abstract","Myeloid cells play an important role in the pathogenesis of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Monocytes, macrophages, and microglia can adopt two distinct phenotypes, with M1-polarized cells being more related to inflammation and autoimmunity while M2-polarized cells contribute to tissue repair and anti-inflammatory processes. Here, we show that deletion of the mineralocorticoid receptor (MR) in bone marrow-derived macrophages and peritoneal macrophages caused their polarization toward the M2 phenotype with its distinct gene expression, altered phagocytic and migratory properties, and dampened NO production. After induction of EAE, mice that are selectively devoid of the MR in their myeloid cells (MRlysM mice) showed diminished clinical symptoms and ameliorated histological hallmarks of neuroinflammation. T cells in peripheral lymphoid organs of these mice produced less pro-inflammatory cytokines while their proliferation and the abundance of regulatory T cells were unaltered. The numbers of inflammatory monocytes and reactive microglia in the central nervous system (CNS) in MRlysM mice were significantly lower and they adopted an M2-polarized phenotype based on their gene expression profile, presumably explaining the ameliorated neuroinflammation. Our results indicate that the MR in myeloid cells plays a critical role for CNS autoimmunity, providing a rational to interfere with diseases such as MS by pharmacologically targeting this receptor."],["dc.identifier.doi","10.3389/fimmu.2017.01319"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14800"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59025"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-3224"],["dc.relation.issn","1664-3224"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Deletion of the Mineralocorticoid Receptor in Myeloid Cells Attenuates Central Nervous System Autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1127"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Annals of Hematology"],["dc.bibliographiccitation.lastpage","1133"],["dc.bibliographiccitation.volume","96"],["dc.contributor.author","Budde, Holger"],["dc.contributor.author","Papert, Susanne"],["dc.contributor.author","Maas, Jens-Holger"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Wulf, Gerald"],["dc.contributor.author","Hasenkamp, Justin"],["dc.contributor.author","Riggert, Joachim"],["dc.contributor.author","Legler, Tobias Joerg"],["dc.date.accessioned","2018-11-07T10:22:22Z"],["dc.date.available","2018-11-07T10:22:22Z"],["dc.date.issued","2017"],["dc.description.abstract","Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment. In this study, patients were monitored for 12 months after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently associated with the occurrence of GvHD in the observation period. However, the largest area under the receiver operating characteristic curve with 0.90 was observed when a 5-parameter biomarker score based on CD4(+) T cells, CD8(+) T cells, CD19(-) CD21(+) precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor was used to predict GvHD. In addition, CD8(+) T cell levels above 2.3% of all mononuclear cells after engraftment may predict relapse-free survival at least for 12 months. In summary, we found a new biomarker panel for prediction of GvHD which is featured by established laboratory assays and high statistical significance. In order to introduce the biomarker panel into routine clinical protocols, we suggest performing a larger multi-center study."],["dc.identifier.doi","10.1007/s00277-017-2999-5"],["dc.identifier.isi","000403078900008"],["dc.identifier.pmid","28447161"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42255"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Springer"],["dc.relation.issn","1432-0584"],["dc.relation.issn","0939-5555"],["dc.title","Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1220"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1233"],["dc.bibliographiccitation.volume","50"],["dc.contributor.author","Kaiser, Tina K."],["dc.contributor.author","Li, Hu"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Feldmann, Claus"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2021-04-14T08:27:15Z"],["dc.date.available","2021-04-14T08:27:15Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Glucocorticoids (GCs) are widely used to treat acute graft‐versus‐host disease (aGvHD) due to their immunosuppressive activity, but they also reduce the beneficial graft‐versus‐leukemia (GvL) effect of the allogeneic T cells contained in the graft. Here, we tested whether aGvHD therapy could be improved by delivering GCs with the help of inorganic–organic hybrid nanoparticles (IOH‐NPs) that preferentially target myeloid cells. IOH‐NPs containing the GC betamethasone (BMP‐NPs) efficiently reduced morbidity, mortality, and tissue damage in a totally MHC mismatched mouse model of aGvHD. Therapeutic activity was lost in mice lacking the GC receptor (GR) in myeloid cells, confirming the cell type specificity of our approach. BMP‐NPs had no relevant systemic activity but suppressed cytokine and chemokine gene expression locally in the small intestine, which presumably explains their mode of action. Most importantly, BMP‐NPs delayed the development of an adoptively transferred B cell lymphoma better than the free drug, although the overall incidence was unaffected. Our findings thus suggest that employing IOH‐NPs could diminish the risk of relapse associated with GC therapy of aGvHD patients while still allowing to efficiently ameliorate the disease."],["dc.description.abstract","Clinical symptoms and histological hallmarks of acute graft‐versus‐host disease in mice are ameliorated by glucocorticoids when specifically delivered to macrophages with the help of nanoparticles. In addition, this therapeutic intervention improves the graft‐versus‐leukemia effect compared to the free drug, and thus presumably reduces the risk of relapse. image"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/eji.201948464"],["dc.identifier.eissn","1521-4141"],["dc.identifier.issn","0014-2980"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82221"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Glucocorticoids delivered by inorganic–organic hybrid nanoparticles mitigate acute graft‐versus‐host disease and sustain graft‐versus‐leukemia activity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Endocrine Reviews"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Furlow, J. David"],["dc.contributor.author","Watson, Monica L."],["dc.contributor.author","Baehr, Leslie M."],["dc.contributor.author","Karbassi, E."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Bodine, Sue C."],["dc.date.accessioned","2018-11-07T08:42:33Z"],["dc.date.available","2018-11-07T08:42:33Z"],["dc.date.issued","2010"],["dc.identifier.isi","000281989401038"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19726"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Endocrine Soc"],["dc.publisher.place","Chevy chase"],["dc.relation.conference","92nd Meeting and Expo of the Endocrine Society (ENDO 2010)"],["dc.relation.eventlocation","San Diego, CA"],["dc.relation.issn","0163-769X"],["dc.title","The Glucocorticoid Receptor and Its Direct Target Gene MuRF1 Are Required for Dexamethasone-Induced Skeletal Muscle Atrophy"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Infection"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Kleiman, Anna"],["dc.contributor.author","Huebner, S."],["dc.contributor.author","Heuer, H."],["dc.contributor.author","Winning, J."],["dc.contributor.author","Berger, S."],["dc.contributor.author","Libert, Claude"],["dc.contributor.author","Weigand, Markus A."],["dc.contributor.author","Schuetz, Guenther"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Bauer, M."],["dc.contributor.author","Tuckermann, Jan P."],["dc.date.accessioned","2018-11-07T08:52:27Z"],["dc.date.available","2018-11-07T08:52:27Z"],["dc.date.issued","2011"],["dc.format.extent","S109"],["dc.identifier.isi","000294888800036"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22165"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Heidelberg"],["dc.relation.issn","0300-8126"],["dc.title","Glucocorticoids control systemic inflammatory response by regulation of energy metabolism and cytokine expression"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Immunology"],["dc.bibliographiccitation.lastpage","53"],["dc.bibliographiccitation.volume","122"],["dc.contributor.author","Lim, Hee-Young"],["dc.contributor.author","Mueller, Nora"],["dc.contributor.author","Herold, Marco J."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:59:00Z"],["dc.date.available","2018-11-07T10:59:00Z"],["dc.date.issued","2007"],["dc.description.abstract","Glucocorticoids (GCs) are involved in the modulation of macrophage function and thereby control the host's immune responses to pathogens. However, neither the role of hormone concentration nor the differential contribution of the glucocorticoid (GR) and the mineralocorticoid receptors (MR) to these activities are known. Here we show that low levels of corticosterone enhance NO production as well as mRNA expression of pro-inflammatory cytokines, chemokines and enzymes required for mediator synthesis. In contrast, at high corticosterone concentrations macrophage function was strongly repressed. Importantly, inactivation of the GR by lentiviral delivery of siRNAs abrogated both the immunostimulatory and the immunosuppressive GC actions whereas inactivation of the MR had no effect. Furthermore, removal of endogenous GCs by adrenalectomy in vivo induced a preactivated state in macrophages that could be modulated by corticosterone. We conclude that GCs exert distinct effects on macrophage function dependent on their concentration, and that they primarily act through the GR despite concomitant expression of the MR."],["dc.identifier.doi","10.1111/j.1365-2567.2007.02611.x"],["dc.identifier.isi","000249040700005"],["dc.identifier.pmid","17451463"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50596"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0019-2805"],["dc.title","Glucocorticoids exert opposing effects on macrophage function dependent on their concentration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]