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","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.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"]]

[["dc.bibliographiccitation.artnumber","1200"],["dc.bibliographiccitation.journal","Frontiers in Immunology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Finck, Tobias L. K."],["dc.contributor.author","Pellkofer, Hannah L."],["dc.contributor.author","Reichardt, Holger M."],["dc.contributor.author","Lühder, Fred"],["dc.date.accessioned","2019-07-09T11:51:45Z"],["dc.date.available","2019-07-09T11:51:45Z"],["dc.date.issued","2019"],["dc.description.abstract","Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by the infiltration of mononuclear cells into the CNS and a subsequent inflammation of the brain.Monocytes are implicated in disease pathogenesis not only in their function as potential antigen-presenting cells involved in the local reactivation of encephalitogenic T cells but also by independent effector functions contributing to structural damage and disease progression. However, monocytes also have beneficial effects as they can exert anti-inflammatory activity and promote tissue repair. Glucocorticoids (GCs) are widely used to treat acute relapses in MS patients. They act on a variety of cell types but their exact mechanisms of action including their modulation of monocyte function are not fully understood. Here we investigated effects of the therapeutically relevant GC methylprednisolone (MP) on monocytes from healthy individuals and MS patients in vitro and in vivo. The monocyte composition in the blood was different in MS patients compared to healthy individuals, but it was only marginally affected byMP treatment. In contrast, application ofMP caused amarked shift toward an anti-inflammatory monocyte phenotype in vitro and in vivo as revealed by an altered gene expression profile. Chemotaxis of monocytes toward CCL2, CCL5, and CX3CL1 was increased in MS patients compared to healthy individuals and further enhanced by MP pulse therapy. Both of these migration-promoting effects were more pronounced in MS patients with an acute relapse than in those with a progressive disease. Interestingly, the pro-migratory GC effect was independent of chemokine receptor levels as exemplified by results obtained for CCR2. Collectively, our findings suggest that GCs polarizemonocytes toward an anti-inflammatory phenotype and enhance their migration into the inflamed CNS, endowing them with the capacity to suppress the pathogenic immune response."],["dc.identifier.doi","10.3389/fimmu.2019.01200"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16184"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60002"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Glucocorticoid Therapy of Multiple Sclerosis Patients Induces Anti-inflammatory Polarization and Increased Chemotaxis of Monocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","731"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","FASEB BioAdvances"],["dc.bibliographiccitation.lastpage","746"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Markov, Alex"],["dc.contributor.author","Kraemer, Lena K."],["dc.contributor.author","Christalla, Peter"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.date.accessioned","2020-01-21T09:29:21Z"],["dc.date.accessioned","2021-10-27T13:22:07Z"],["dc.date.available","2020-01-21T09:29:21Z"],["dc.date.available","2021-10-27T13:22:07Z"],["dc.date.issued","2019"],["dc.description.abstract","Satellite cells reside in defined niches and are activated upon skeletal muscle injury to facilitate regeneration. Mechanistic studies of skeletal muscle regeneration are hampered by the inability to faithfully simulate satellite cell biology in vitro. We sought to overcome this limitation by developing tissue engineered skeletal muscle (ESM) with (1) satellite cell niches and (2) the capacity to regenerate after injury. ESMs contained quiescent Pax7‐positive satellite cells in morphologically defined niches. Satellite cells could be activated to repair (i) cardiotoxin and (ii) mechanical crush injuries. Activation of the Wnt‐pathway was essential for muscle regeneration. Finally, muscle progenitors from the engineered niche developed de novo ESM in vitro and regenerated skeletal muscle after cardiotoxin‐induced injury in vivo. We conclude that ESM with functional progenitor niches reminiscent of the in vivo satellite cell niches can be engineered in vitro. ESM may ultimately be exploited in disease modeling, drug screening, or muscle regeneration."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2019"],["dc.identifier.doi","10.1096/fba.2019-00013"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17135"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92070"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2573-9832"],["dc.relation.issn","2573-9832"],["dc.relation.issn","2573-9832"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","Regeneration competent satellite cell niches in rat engineered skeletal muscle"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2480"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","STEM CELLS"],["dc.bibliographiccitation.lastpage","2491"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Zafiriou, Maria Patapia"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Pavlova, Elena"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Reichardt, Holger M."],["dc.contributor.author","Bergmann, Martin W."],["dc.contributor.author","El-Armouche, Ali"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Zelarayan, Laura Cecilia"],["dc.date.accessioned","2017-09-07T11:45:36Z"],["dc.date.available","2017-09-07T11:45:36Z"],["dc.date.issued","2014"],["dc.description.abstract","The role of erythropoietin (Epo) in myocardial repair after infarction remains inconclusive. We observed high Epo receptor (EPOR) expression in cardiac progenitor cells (CPCs). Therefore, we aimed to characterize these cells and elucidate their contribution to myocardial regeneration on Epo stimulation. High EPOR expression was detected during murine embryonic heart development followed by a marked decrease until adulthood. EPOR-positive cells in the adult heart were identified in a CPC-enriched cell population and showed coexpression of stem, mesenchymal, endothelial, and cardiomyogenic cell markers. We focused on the population coexpressing early (TBX5, NKX2.5) and definitive (myosin heavy chain [MHC], cardiac Troponin T [cTNT]) cardiomyocyte markers. Epo increased their proliferation and thus were designated as Epo-responsive MHC expressing cells (EMCs). In vitro, EMCs proliferated and partially differentiated toward cardiomyocyte-like cells. Repetitive Epo administration in mice with myocardial infarction (cumulative dose 4 IU/g) resulted in an increase in cardiac EMCs and cTNT-positive cells in the infarcted area. This was further accompanied by a significant preservation of cardiac function when compared with control mice. Our study characterized an EPO-responsive MHC-expressing cell population in the adult heart. Repetitive, moderate-dose Epo treatment enhanced the proliferation of EMCs resulting in preservation of post-ischemic cardiac function."],["dc.identifier.doi","10.1002/stem.1741"],["dc.identifier.gro","3142066"],["dc.identifier.isi","000341294500017"],["dc.identifier.pmid","24806289"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12130"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4167"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/77"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A02: Bedeutung des Phosphatase-Inhibitors-1 für die SR-spezifische Modulation der Beta- adrenozeptor-Signalkaskade"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation.eissn","1549-4918"],["dc.relation.issn","1066-5099"],["dc.relation.workinggroup","RG El-Armouche"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Erythropoietin Responsive Cardiomyogenic Cells Contribute to Heart Repair Post Myocardial Infarction"],["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"]]