Schweingruber, Nils

[["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","174"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuroendocrinology"],["dc.bibliographiccitation.lastpage","182"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Schweingruber, Nils"],["dc.contributor.author","Reichardt, Sybille D."],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T09:15:58Z"],["dc.date.available","2018-11-07T09:15:58Z"],["dc.date.issued","2012"],["dc.description.abstract","Glucocorticoids (GCs) are widely used to treat inflammatory diseases such as multiple sclerosis (MS). They predominantly act through the GC receptor, a member of the nuclear receptor superfamily that controls transcription by several different mechanisms. Owing to its ubiquitous expression, there are a variety of cell types that could serve as GC targets in the pathogenesis and treatment of MS. This brings about a great diversity of mechanisms potentially involved in the modulation of neuroinflammation by GCs, including the induction of apoptosis, repression of pro-inflammatory mediators and the expansion of myeloid-derived suppressor cells. Nevertheless, it is not well understood which of these mechanisms are essential for therapeutic efficacy. In this review, we summarise findings made concerning the actions of GCs in MS and its animal model experimental autoimmune encephalomyelitis, and also elucidate current concepts and developments that pertain to this clinically highly relevant treatment regimen."],["dc.identifier.doi","10.1111/j.1365-2826.2011.02161.x"],["dc.identifier.isi","000298601800016"],["dc.identifier.pmid","21615563"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27832"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0953-8194"],["dc.title","Mechanisms of Glucocorticoids in the Control of Neuroinflammation"],["dc.type","review"],["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.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","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"]]