Fischer, Henrike J.

[["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","99"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Molecular and Cellular Endocrinology"],["dc.bibliographiccitation.lastpage","107"],["dc.bibliographiccitation.volume","380"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:17:40Z"],["dc.date.available","2018-11-07T09:17:40Z"],["dc.date.issued","2013"],["dc.description.abstract","Glucocorticoids (GCs) are the most commonly prescribed drugs for the treatment of acute disease bouts in multiple sclerosis (MS) patients. While T lymphocytes were shown to be essential targets of GC therapy, at least in animal models of MS, the mechanisms by which GCs modulate T cell function are less clear. Until now, apoptosis induction and repression of pro-inflammatory cytokines in T cells have been considered the most critical mechanisms in ameliorating disease symptoms. However, this notion is being challenged by increasing evidence that the control of T cell migration and chemotaxis by GCs might be even more important for the treatment of neuroinflammatory diseases. In this review we aim to provide an overview of how GCs impact the morphological alterations that T cells undergo during activation and migration as well as the influences that GCs have on the directed movement of T cells under the influence of chemokines. A deeper understanding of these processes should not only help to advance our understanding of how GCs exert their beneficial effects in MS therapy but may reveal future strategies to intervene in the pathogenesis of neuroinflammatory diseases. (C) 2013 Elsevier Ireland Ltd. All rights reserved."],["dc.description.sponsorship","DFG [Lu634/8-1, SFB-TRR 43/B11, SFB-TRR 43/B13]"],["dc.identifier.doi","10.1016/j.mce.2013.04.001"],["dc.identifier.isi","000326912400011"],["dc.identifier.pmid","23578583"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28221"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Ireland Ltd"],["dc.relation.issn","0303-7207"],["dc.title","The potential role of T cell migration and chemotaxis as targets of glucocorticoids in multiple sclerosis and 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","17"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","27"],["dc.bibliographiccitation.volume","260"],["dc.contributor.author","Camara, Monika"],["dc.contributor.author","Beyersdorf, Niklas"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Herold, Marco J."],["dc.contributor.author","Ip, Chi Wang"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Toyka, Klaus V."],["dc.contributor.author","Taurog, Joel D."],["dc.contributor.author","Huenig, Thomas"],["dc.contributor.author","Herrmann, Thomas R."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Weishaupt, Andreas"],["dc.contributor.author","Kerkau, Thomas"],["dc.date.accessioned","2018-11-07T09:22:23Z"],["dc.date.available","2018-11-07T09:22:23Z"],["dc.date.issued","2013"],["dc.description.abstract","The role of CD8(+) T cells in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is still unclear. We describe here significantly reduced disease activity of EAE both in Lewis rats, depleted of CD8(+) T cells by monoclonal antibodies and CD8 knockout rats, which was accompanied by reduced leukocyte infiltration into the spinal cord. We detected myelin basic protein (MBP)-specific CD4(+) T cells in peripheral lymphoid organs of CD8-depleted animals which, however, failed to differentiate into interferon-gamma-producing effector cells. Our results indicate that CD8(+) T cells interact with myelin-specific CD4(+) T cells early in EAE enabling them to differentiate into pathogenic effector cells. (C) 2013 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.jneuroim.2013.04.014"],["dc.identifier.isi","000321093000003"],["dc.identifier.pmid","23664330"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29330"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-5728"],["dc.title","CD8(+) T cell help is required for efficient induction of EAE in Lewis rats"],["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 Journal"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Finck, T. L. K."],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T09:35:28Z"],["dc.date.available","2018-11-07T09:35:28Z"],["dc.date.issued","2014"],["dc.format.extent","320"],["dc.identifier.isi","000354441300732"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32386"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Ltd"],["dc.publisher.place","London"],["dc.relation.conference","Joint ACTRIMS-ECTRIMS Meeting"],["dc.relation.eventlocation","Boston, MA"],["dc.relation.issn","1477-0970"],["dc.relation.issn","1352-4585"],["dc.title","Impact of glucocorticoid treatment on the migration and polarization of human monocytes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","26"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.lastpage","32"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Lingner, Thomas"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Weishaupt, Andreas"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:19:23Z"],["dc.date.available","2018-11-07T10:19:23Z"],["dc.date.issued","2016"],["dc.description.abstract","MS is a highly prevalent neuroinflammatory disease of presumed autoimmune origin. Clinical observations and animal studies suggest that CD8(+) T cells play an important role in MS but their exact mechanisms are ill defined. When we actively induced EAE in CD8 knock-out DA rats, or adoptively transferred encephalitogenic CD4(+) T cells into CD8 knock-out DA rats, the disease course was indistinguishable from controls. Since our previous findings had revealed that the absence of CD8(+) T cells in Lewis rats ameliorated EAE, we compared antigen-induced T cell differentiation in both strains. Disease onset and the composition of the draining lymph nodes were similar but T cell activation in DA rats was much weaker. Moreover, oligoclonal expansion of CD8(+) T cells was exclusively observed in Lewis but not in DA rats. This suggests that myelin-specific CD8(+) T cells are involved in the differentiation of encephalitogenic CD4(+) T cells in Lewis rats, whilst they do not impact CD4(+) T cell priming in DA rats. Hence, clonal expansion of CD8(+) T cells in secondary lymphoid organs appears to be linked to their ability to modulate CNS autoimmune responses. (C) 2015 Published by Elsevier B.V."],["dc.description.sponsorship","German Research Foundation (DFG) [SFB/TRR 43]"],["dc.identifier.doi","10.1016/j.jneuroim.2015.10.020"],["dc.identifier.isi","000368955000005"],["dc.identifier.pmid","26711565"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41645"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1872-8421"],["dc.relation.issn","0165-5728"],["dc.title","Modulation of CNS autoimmune responses by CD8(+) T cells coincides with their oligoclonal expansion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.volume","275"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Huppke, Peter"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:33:34Z"],["dc.date.available","2018-11-07T09:33:34Z"],["dc.date.issued","2014"],["dc.format.extent","60"],["dc.identifier.doi","10.1016/j.jneuroim.2014.08.157"],["dc.identifier.isi","000345192100150"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31994"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","12th International Congress of Neuroimmunology (ISNI)"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","1872-8421"],["dc.relation.issn","0165-5728"],["dc.title","Novel mechanisms of glucocorticoids in the treatment of multiple sclerosis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.volume","253"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Fischer, Lisa"],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Fischer, Henrike"],["dc.contributor.author","Karabinskya, Anna"],["dc.contributor.author","Reichardt, Holger"],["dc.date.accessioned","2018-11-07T09:02:16Z"],["dc.date.available","2018-11-07T09:02:16Z"],["dc.date.issued","2012"],["dc.identifier.isi","000312764800195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24641"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Boston, MA"],["dc.title","Altered T cell migration rather than induction of apoptosis is essential for glucocorticoid therapy of experimental autoimmune encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.volume","253"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:02:15Z"],["dc.date.available","2018-11-07T09:02:15Z"],["dc.date.issued","2012"],["dc.format.extent","46"],["dc.identifier.isi","000312764800124"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24639"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.conference","11th International Congress of Neuroimmunology (ISNI)"],["dc.relation.eventlocation","Boston, MA"],["dc.relation.issn","0165-5728"],["dc.title","Gimap5 deficiency in Lewis rats causes lymphopenia and exacerbates 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","15437"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","15450"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Baake, Tina"],["dc.contributor.author","Jörß, Katharina"],["dc.contributor.author","Suennemann, Jennifer"],["dc.contributor.author","Roßmann, Laura"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Reichardt, Holger M."],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Reichardt, Sybille D."],["dc.date.accessioned","2019-07-09T11:45:14Z"],["dc.date.available","2019-07-09T11:45:14Z"],["dc.date.issued","2018"],["dc.description.abstract","Graft-versus-host disease (GvHD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), which is caused by allogeneic T cells recognizing molecules of the recipient as foreign. Endogenous glucocorticoids (GC) released from the adrenal gland are crucial in regulating such inflammatory diseases. Here we demonstrate that genetically engineered mice, that are largely unresponsive to GC, suffer from aggravated clinical symptoms and increased mortality after HSCT, effects that could be tempered by neutralization of IL-6. Interestingly, selective ablation of the GC receptor (GR) in recipient myeloid cells resulted in fulminant disease as well. While histopathological analysis of the jejunum failed to reveal any differences between sick mice of both genotypes, systemic IL-6 and TNFα secretion was strongly increased in transplanted mice lacking the GR in myeloid cells briefly before the majority of them succumbed to the disease. Collectively, our findings reveal an important role of the GR in recipient cells in limiting the cytokine storm caused by GvHD induction."],["dc.identifier.doi","10.18632/oncotarget.24602"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15071"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59189"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject.ddc","610"],["dc.title","The glucocorticoid receptor in recipient cells keeps cytokine secretion in acute graft-versus-host disease at bay"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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"]]