Lühder, Fred

[["dc.bibliographiccitation.journal","Wiener klinische Wochenschrift"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Wuest, S."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Reichardt, M."],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T11:12:50Z"],["dc.date.available","2018-11-07T11:12:50Z"],["dc.date.issued","2008"],["dc.format.extent","52"],["dc.identifier.isi","000259367100164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53751"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.issn","0043-5325"],["dc.title","Peripheral T cells are the therapeutic targets of high-dose glucocorticoids in experimental autoimmune encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1041"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","American Journal Of Pathology"],["dc.bibliographiccitation.lastpage","1053"],["dc.bibliographiccitation.volume","170"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","McPherson, Kirsty G."],["dc.contributor.author","de Graaf, Katrien L."],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Wiehr, Stefan"],["dc.contributor.author","Herrmann, Thomas R."],["dc.contributor.author","Weissert, Robert"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T11:04:12Z"],["dc.date.available","2018-11-07T11:04:12Z"],["dc.date.issued","2007"],["dc.description.abstract","To study the effect of enhanced glucocorticoid signaling on T cells, we generated transgenic rats overexpressmig a mutant glucocorticoid receptor with increased ligand affinity in the thymus. We found that this caused massive thymocyte apoptosis at physiological hormone levels, which could be reversed by adrenalectomy. Due to homeostatic proliferation, a considerable number of mature T lymphocytes accumulated in the periphery, responding normally to costimulation but exhibiting a perturbed T-cell repertoire. Furthermore, the transgenic rats showed increased resistance to experimental autoimmune encephalomyelitis, which manifests in a delayed onset and milder disease course, impaired leukocyte infiltration into the central nervous system and a distinct cytokine profile. in contrast, the ability of the transgenic rats to mount an allergic airway response to ovalbumin was not compromised, although isotype switching of antigen-specific immunoglobulins was altered. Collectively, our findings suggest that endogenous glucocorticoids impact T-cell development and favor the selection of Th2- over TH1-dominated adaptive immune responses."],["dc.identifier.doi","10.2353/ajpath.2007.060804"],["dc.identifier.isi","000244574500024"],["dc.identifier.pmid","17322387"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/51781"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Investigative Pathology, Inc"],["dc.relation.issn","0002-9440"],["dc.title","Enhanced glucocorticoid receptor signaling in T cells impacts thymocyte apoptosis and adaptive immune responses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1326"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1338"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Flach, Anne-Christine"],["dc.contributor.author","Litke, Tanja"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Lingner, Thomas"],["dc.contributor.author","Bommhardt, Ursula"],["dc.contributor.author","Sendtner, Michael"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T09:57:51Z"],["dc.date.available","2018-11-07T09:57:51Z"],["dc.date.issued","2015"],["dc.description.abstract","Brain-derived neurotrophic factor (BDNF) promotes neuronal survival, regeneration, and plasticity. Emerging evidence also indicates an essential role for BDNF outside the nervous system, for instance in immune cells. We therefore investigated the impact of BDNF on Tcells using BDNF knockout (KO) mice and conditional KO mice lacking BDNF specifically in this lymphoid subset. In both settings, we observed diminished T-cell cellularity in peripheral lymphoid organs and an increase in CD4(+)CD44(+) memory Tcells. Analysis of thymocyte development revealed diminished total thymocyte numbers, accompanied by a significant increase in CD4/CD8 double-negative (DN) thymocytes due to a partial block in the transition from the DN3 to the DN4 stage. This was neither due to increased thymocyte apoptosis nor defects in the expression of the TCR- chain or the pre-TCR. In contrast, pERK but not pAKT levels were diminished in DN3 BDNF-deficient thymocytes. BDNF deficiency in Tcells did not result in gross deficits in peripheral acute immune responses nor in changes of the homeostatic proliferation of peripheral Tcells. Taken together, our data reveal a critical autocrine and/or paracrine role of T-cell-derived BDNF in thymocyte maturation involving ERK-mediated TCR signaling pathways."],["dc.identifier.doi","10.1002/eji.201444985"],["dc.identifier.isi","000354182300006"],["dc.identifier.pmid","25627579"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37248"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","Thymocyte-derived BDNF influences T-cell maturation at the DN3/DN4 transition stage"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4310"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","4318"],["dc.bibliographiccitation.volume","187"],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Haine, Axel"],["dc.contributor.author","Tiede, Karsten"],["dc.contributor.author","Karabinskaya, Anna"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Wuest, Simone"],["dc.contributor.author","Metselaar, Josbert M."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T08:50:42Z"],["dc.date.available","2018-11-07T08:50:42Z"],["dc.date.issued","2011"],["dc.description.abstract","Glucocorticoids (GCs) are widely used to treat acute relapses of multiple sclerosis (MS). In this study, we demonstrate that liposomal encapsulation augments the therapeutic potency of GCs as they ameliorate experimental autoimmune encephalomyelitis (EAE) to the same extent as free GC, but at strongly reduced dosage and application frequency. Importantly, this is accompanied by an altered mode of action. Unlike free GCs, which mainly target T lymphocytes during EAE therapy, liposomal GCs only marginally affect T cell apoptosis and function. In contrast, liposomal GCs efficiently repress proinflammatory macrophage functions and upregulate anti-inflammatory genes associated with the alternatively activated M2 phenotype. The GC receptor (GR) per se is indispensable for the therapeutic efficacy of liposomal GC. In contrast to free GCs, however, the individual deletion of the GR either in T cells or myeloid cells has little effect on the efficacy of liposomal GCs in the treatment of EAE. Only the combined deletion of the GR in both cellular compartments markedly compromises the therapeutic effect of liposomal GCs on disease progression. In conclusion, encapsulation of GC does not only enhance their efficacy in the treatment of EAE but also alters their target cell specificity and their mode of action compared with free GCs. The Journal of Immunology, 2011, 187: 4310-4318."],["dc.identifier.doi","10.4049/jimmunol.1101604"],["dc.identifier.isi","000295623100043"],["dc.identifier.pmid","21918186"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21754"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Liposomal Encapsulation of Glucocorticoids Alters Their Mode of Action in the Treatment of Experimental Autoimmune Encephalomyelitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2361"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","2370"],["dc.bibliographiccitation.volume","39"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Weishaupt, Andreas"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Herold, Marco J."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T11:24:50Z"],["dc.date.available","2018-11-07T11:24:50Z"],["dc.date.issued","2009"],["dc.description.abstract","Autoimmune responses in the CNS can be induced by adoptive transfer of CD4(+) T effector cells after antigen-restimulation and expansion of clonal cell lines in vitro. However, pathogenic factors remain partially elusive due to the lack of appropriate methods to achieve gene inactivation. Here we describe a protocol for stable gene silencing in differentiated rat T cells by retroviral transfer of small hairpin RNAs. Through the combination of an expression cassette containing the green fluorescent protein with a puromycin selection cassette this allows for the generation of pure knockdown cell lines suitable for tracking in animals. Exemplified for the glucocorticoid. receptor, we demonstrate that gene silencing renders T effector cells unresponsive to ligand-induced apoptosis and gene regulation without affecting their ability to induce EAE in rats. interestingly, glucocorticoid administration remains effective in the treatment of EAE despite strongly diminished glucocorticoid receptor expression in antigen-specific T cells. This highlights an important role of other cell types and bystander T cells as targets of glucocorticoid therapy. Collectively, our approach provides a simple tool for stable and efficient gene silencing in T effector cells, which should help to better understand brain autoimmune pathophysiology."],["dc.description.sponsorship","Gemeinnutzige Hertie-Stiftung [1.01.1/06/010]; DFG [Re1631/1-3]"],["dc.identifier.doi","10.1002/eji.200939490"],["dc.identifier.isi","000269786000009"],["dc.identifier.pmid","19676075"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56491"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","0014-2980"],["dc.title","Stable silencing of the glucocorticoid receptor in myelin-specific T effector cells by retroviral delivery of shRNA: Insight into neuroinflammatory disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","417017"],["dc.bibliographiccitation.journal","International Journal of Endocrinology"],["dc.contributor.author","Wuest, Simone"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T09:14:43Z"],["dc.date.available","2018-11-07T09:14:43Z"],["dc.date.issued","2012"],["dc.description.abstract","Glucocorticoids (GCs) represent the standard treatment for acute disease bouts in multiple sclerosis (MS) patients, for which methylprednisolone (MP) pulse therapy is the most frequently used protocol. Here, we compared the efficacy of therapeutic and preventive MP application in MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE) in C57Bl/6 mice. When administered briefly after the onset of the disease, MP efficiently ameliorated EAE in a dose-dependent manner. Surprisingly, MP administration around the time of immunization was contraindicated as it even increased leukocyte infiltration into the CNS and worsened the disease symptoms. Our analyses suggest that in the latter case an incomplete depletion of peripheral T cells by MP triggers homeostatic proliferation, which presumably results in an enhanced priming of autoreactive T cells and causes an aggravated disease course. Thus, the timing and selection of a particular GC derivative require careful consideration in MS therapy."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1155/2012/417017"],["dc.identifier.isi","000312031800001"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8391"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27487"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Hindawi Publishing Corporation"],["dc.relation.issn","1687-8337"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Preventive Treatment with Methylprednisolone Paradoxically Exacerbates Experimental Autoimmune Encephalomyelitis"],["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","713"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","729"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Fischer, Lisa"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Karabinskaya, Anna"],["dc.contributor.author","Labi, Verena"],["dc.contributor.author","Villunger, Andreas"],["dc.contributor.author","Kretzschmar, Benedikt"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:40:54Z"],["dc.date.available","2018-11-07T09:40:54Z"],["dc.date.issued","2014"],["dc.description.abstract","Glucocorticoids (GCs) are the standard therapy for treating multiple sclerosis (MS) patients suffering from an acute relapse. One of the main mechanisms of GC action is held to be the induction of T cell apoptosis leading to reduced lymphocyte infiltration into the CNS, yet our analysis of experimental autoimmune encephalomyelitis (EAE) in three different strains of genetically manipulated mice has revealed that the induction of T cell apoptosis is not essential for the therapeutic efficacy of GCs. Instead, we identified the redirection of T cell migration in response to chemokines as a new therapeutic principle of GC action. GCs inhibited the migration of T cells towards CCL19 while they enhanced their responsiveness towards CXCL12. Importantly, blocking CXCR4 signaling in vivo by applying Plerixafor(A (R)) strongly impaired the capacity of GCs to interfere with EAE, as revealed by an aggravated disease course, more pronounced CNS infiltration and a more dispersed distribution of the infiltrating T cells throughout the parenchyma. Our observation that T cells lacking the GC receptor were refractory to CXCL12 further underscores the importance of this pathway for the treatment of EAE by GCs. Importantly, methylprednisolone pulse therapy strongly increased the capacity of peripheral blood T cells from MS patients of different subtypes to migrate towards CXCL12. This indicates that modulation of T cell migration is an important mechanistic principle responsible for the efficacy of high-dose GC therapy not only of EAE but also of MS."],["dc.identifier.doi","10.1007/s00401-014-1248-4"],["dc.identifier.isi","000334426300007"],["dc.identifier.pmid","24488308"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33606"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.title","Chemokine-mediated redirection of T cells constitutes a critical mechanism of glucocorticoid therapy in autoimmune CNS responses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","MULTIPLE SCLEROSIS"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Wuest, Simone"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T11:11:47Z"],["dc.date.available","2018-11-07T11:11:47Z"],["dc.date.issued","2008"],["dc.format.extent","S248"],["dc.identifier.isi","000259675700816"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53512"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.conference","13th Annual Meeting of the Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/24th Congress of the European-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis/5th Congress of the Latin-Amer-Comm-for-Treatment-and-Res-in-Multiple-Sclerosis"],["dc.relation.eventlocation","Montreal, CANADA"],["dc.relation.issn","1352-4585"],["dc.title","Peripheral T cells are the therapeutic targets of high dose glucocorticoids in experimental autoimmune encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4509"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","4516"],["dc.bibliographiccitation.volume","187"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Theiss, Jennifer"],["dc.contributor.author","Karabinskaya, Anna"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Karow, Ulrike"],["dc.contributor.author","Herold, Marco J."],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Utermoehlen, Olaf"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T08:50:13Z"],["dc.date.available","2018-11-07T08:50:13Z"],["dc.date.issued","2011"],["dc.description.abstract","The activity of acid sphingomyelinase (aSMase) was previously reported to be involved in glucocorticoid-induced cell death (GICD) of T lymphocytes. This mechanism in turn is believed to contribute to the therapeutic efficacy of glucocorticoids (GCs) in the treatment of inflammatory diseases. In this study, we reassessed the role of aSMase in GICD by using aSMase knockout mice. The absence of aSMase largely abolished the partial protection that effector memory CD4(+) T cells in wild-type mice possess against GICD. Reduced IL-2 secretion by aSMase-deficient CD4(+) T cells suggested that a lack of this important survival factor might be the cause of these cells' enhanced susceptibility to GICD. Indeed, addition of IL-2 restored the protection against GICD, whereas neutralization of IL-2 abrogated the otherwise protective effect seen in wild-type effector memory CD4(+) T cells. The therapeutic implications of the altered sensitivity of aSMase-deficient T cells to GICD were assessed in models of inflammatory disorders; namely, experimental autoimmune encephalomyelitis and acute graft-versus-host disease. Surprisingly, GC treatment was equally efficient in both models in terms of ameliorating the diseases, regardless of the genotype of the T cells. Thus, our data reveal a hitherto unrecognized contribution of aSMase to the sensitivity of effector memory CD4(+) T cells to GICD and call into question the traditionally attributed importance of GICD of T cells to the treatment of inflammatory diseases by GCs. The Journal of Immunology, 2011, 187: 4509-4516."],["dc.identifier.doi","10.4049/jimmunol.1100911"],["dc.identifier.isi","000296496000017"],["dc.identifier.pmid","21948986"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21648"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","0022-1767"],["dc.title","Acid Sphingomyelinase Is Required for Protection of Effector Memory T Cells against Glucocorticoid-Induced Cell Death"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Clinical Immunology"],["dc.bibliographiccitation.volume","131"],["dc.contributor.author","Linker, Ralf"],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Brandt, Jens van den"],["dc.contributor.author","Reichardt, Holger"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T08:34:08Z"],["dc.date.available","2018-11-07T08:34:08Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1016/j.clim.2009.03.328"],["dc.identifier.isi","000266342300320"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17749"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.publisher.place","San diego"],["dc.relation.conference","9th Annual Meeting of the Federation-of-Clinical-Immunology-Societies"],["dc.relation.eventlocation","San Francisco, CA"],["dc.title","Critical Role of the Neurotrophic Factor BDNF in T Cell Development"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]