Regen, Tommy

[["dc.bibliographiccitation.firstpage","447"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.lastpage","458"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Schnaars, Mareike"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Krishnamoorthy, Gurumoorthy"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Bakhti, Mostafa"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T08:59:39Z"],["dc.date.available","2018-11-07T08:59:39Z"],["dc.date.issued","2011"],["dc.description.abstract","The transfer of antigens from oligodendrocytes to immune cells has been implicated in the pathogenesis of autoimmune diseases. Here, we show that oligodendrocytes secrete small membrane vesicles called exosomes, which are specifically and efficiently taken up by microglia both in vitro and in vivo. Internalisation of exosomes occurs by a macropinocytotic mechanism without inducing a concomitant inflammatory response. After stimulation of microglia with interferon-gamma, we observe an upregulation of MHC class II in a subpopulation of microglia. However, exosomes are preferentially internalised in microglia that do not seem to have antigen-presenting capacity. We propose that the constitutive macropinocytotic clearance of exosomes by a subset of microglia represents an important mechanism through which microglia participate in the degradation of oligodendroglial membrane in an immunologically 'silent' manner. By designating the capacity for macropinocytosis and antigen presentation to distinct cells, degradation and immune function might be assigned to different subtypes of microglia."],["dc.description.sponsorship","ERC; EMBO YIP; German Research Council [SFB/TR43]"],["dc.identifier.doi","10.1242/jcs.074088"],["dc.identifier.isi","000286223600016"],["dc.identifier.pmid","21242314"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8034"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23953"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Company Of Biologists Ltd"],["dc.relation.issn","0021-9533"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis"],["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","411"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","424"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Pfoertner, Ramona"],["dc.contributor.author","Pham, Trinh"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Hayardeny, Liat"],["dc.contributor.author","Piryatinsky, Victor"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Rossum, Denise van"],["dc.contributor.author","Brakelmann, Lars"],["dc.contributor.author","Hagemeier, Karin"],["dc.contributor.author","Kuhlmann, Tanja"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","John, Gareth R."],["dc.contributor.author","Kramann, Nadine"],["dc.contributor.author","Wegner, Christiane"],["dc.date.accessioned","2018-11-07T09:06:50Z"],["dc.date.available","2018-11-07T09:06:50Z"],["dc.date.issued","2012"],["dc.description.abstract","Laquinimod (LAQ) is a new oral immunomodulatory compound that reduces relapse rate, brain atrophy and disability progression in multiple sclerosis (MS). LAQ has well-documented effects on inflammation in the periphery, but little is known about its direct activity within the central nervous system (CNS). To elucidate the impact of LAQ on CNS-intrinsic inflammation, we investigated the effects of LAQ on cuprizone-induced demyelination in mice in vivo and on primary CNS cells in vitro. Demyelination, inflammation, axonal damage and glial pathology were evaluated in LAQ-treated wild type and Rag-1-deficient mice after cuprizone challenge. Using primary cells we tested for effects of LAQ on oligodendroglial survival as well as on cytokine secretion and NF-kappa B activation in astrocytes and microglia. LAQ prevented cuprizone-induced demyelination, microglial activation, axonal transections, reactive gliosis and oligodendroglial apoptoses in wild type and Rag-1-deficient mice. LAQ significantly decreased pro-inflammatory factors in stimulated astrocytes, but not in microglia. Oligodendroglial survival was not affected by LAQ in vitro. Astrocytic, but not microglial, NF-kappa B activation was markedly reduced by LAQ as evidenced by NF-kappa B reporter assay. LAQ also significantly decreased astrocytic NF-kappa B activation in cuprizone-treated mice. Our data indicate that LAQ prevents cuprizone-induced demyelination by attenuating astrocytic NF-kappa B activation. These effects are CNS-intrinsic and not mediated by peripheral immune cells. Therefore, LAQ downregulation of the astrocytic pro-inflammatory response may be an important mechanism underlying its protective effects on myelin, oligodendrocytes and axons. Modulation of astrocyte activation may be an attractive therapeutic target to prevent tissue damage in MS."],["dc.identifier.doi","10.1007/s00401-012-1009-1"],["dc.identifier.isi","000307757200010"],["dc.identifier.pmid","22766690"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9468"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25641"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0001-6322"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Reduced astrocytic NF-kappa B activation by laquinimod protects from cuprizone-induced demyelination"],["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","1477"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1489"],["dc.bibliographiccitation.volume","58"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Lohaus, Raphaela"],["dc.contributor.author","Bayanga, Kathrin"],["dc.contributor.author","Heermann, Stephan"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Hoffmann, Anja"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Bechmann, Ingo"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.date.accessioned","2018-11-07T08:39:43Z"],["dc.date.available","2018-11-07T08:39:43Z"],["dc.date.issued","2010"],["dc.description.abstract","Although there is increasing evidence that blood-derived macrophages support tumor progression, it is still unclear whether specialized resident macrophages, such as brain microglia, also play a prominent role in metastasis formation. Here, we show that microglia enhance invasion and colonization of brain tissue by breast cancer cells, serving both as active transporters and guiding rails. This is antagonized by inactivation of microglia as well as by the Wnt inhibitor Dickkopf-2. Proinvasive microglia demonstrate altered morphology, but neither upregulation of M2-like cytokines nor differential gene expression. Bacterial lipopolysacharide shifts tumor-educated microglia into a classical M1 phenotype, reduces their proinvasive function, and unmasks inflammatory and Wnt signaling as the most strongly regulated pathways. Histological findings in human brain metastases underline the significance of these results. In conclusion, microglia are critical for the successful colonization of the brain by epithelial cancer cells, suggesting inhibition of proinvasive microglia as a promising antimetastatic strategy. (C) 2010 Wiley-Liss, Inc."],["dc.description.sponsorship","German Research Council (DFG) [For942 BI 703/3-1]"],["dc.identifier.doi","10.1002/glia.21022"],["dc.identifier.isi","000280349900008"],["dc.identifier.pmid","20549749"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6326"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19065"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0894-1491"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Microglia Promote Colonization of Brain Tissue by Breast Cancer Cells in a Wnt-Dependent Way"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1000836"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS Pathogens"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Flatz, Lukas"],["dc.contributor.author","Rieger, Toni"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Bergthaler, Andreas"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Schedensack, Mariann"],["dc.contributor.author","Bestmann, Lukas"],["dc.contributor.author","Verschoor, Admar"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Guenther, Stephan"],["dc.contributor.author","Pinschewer, Daniel D."],["dc.date.accessioned","2018-11-07T08:45:46Z"],["dc.date.available","2018-11-07T08:45:46Z"],["dc.date.issued","2010"],["dc.description.abstract","Lassa virus (LASV), the causative agent of Lassa fever (LF), is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I) failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development."],["dc.identifier.doi","10.1371/journal.ppat.1000836"],["dc.identifier.isi","000277720400040"],["dc.identifier.pmid","20360949"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6892"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/20525"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7366"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","T Cell-Dependence of Lassa Fever Pathogenesis"],["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","557"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Infection and Immunity"],["dc.bibliographiccitation.lastpage","564"],["dc.bibliographiccitation.volume","77"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Ebert, Sandra"],["dc.contributor.author","Czesnik, Dirk"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Zeug, Andre"],["dc.contributor.author","Bukowski, Stephanie"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Eiffert, Helmut"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Hammerschmidt, Sven"],["dc.contributor.author","Nau, Roland"],["dc.date.accessioned","2018-11-07T08:34:37Z"],["dc.date.available","2018-11-07T08:34:37Z"],["dc.date.issued","2009"],["dc.description.abstract","Meningitis and meningoencephalitis caused by Escherichia coli are associated with high rates of mortality. When an infection occurs, Toll-like receptors (TLRs) expressed by microglial cells can recognize pathogen-associated molecular patterns and activate multiple steps in the inflammatory response that coordinate the brain's local defense, such as phagocytosis of invading pathogens. An upregulation of the phagocytic ability of reactive microglia could improve the host defense in immunocompromised patients against pathogens such as E. coli. Here, murine microglial cultures were stimulated with the TLR agonists Pam(3)CSK(4) (TLR1/TLR2), lipopolysaccharide (TLR4), and CpG oligodeoxynucleotide (TLR9) for 24 h. Upon stimulation, levels of tumor necrosis factor alpha and the neutrophil chemoattractant CXCL1 were increased, indicating microglial activation. Phagocytic activity was studied after adding either E. coli DH5 alpha or E. coli K1 strains. After 60 and 90 min of bacterial exposure, the number of ingested bacteria was significantly higher in cells prestimulated with TLR agonists than in unstimulated controls (P < 0.01). Addition of cytochalasin D, an inhibitor of actin polymerization, blocked >90% of phagocytosis. We also analyzed the ability of microglia to kill the ingested E. coli strains. Intracellularly surviving bacteria were quantified at different time points (90, 150, 240, and 360 min) after 90 min of phagocytosis. The number of bacteria killed intracellularly after 6 h was higher in cells primed with the different TLR agonists than in unstimulated microglia. Our data suggest that microglial stimulation by the TLR system can increase bacterial phagocytosis and killing. This approach could improve central nervous system resistance to infections in immunocompromised patients."],["dc.identifier.doi","10.1128/IAI.00903-08"],["dc.identifier.isi","000262776100058"],["dc.identifier.pmid","18981243"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7765"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17860"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Microbiology"],["dc.relation.issn","0019-9567"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Toll-Like Receptor Prestimulation Increases Phagocytosis of Escherichia coli DH5 alpha and Escherichia coli K1 Strains by Murine Microglial Cells"],["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"]]