Lodygin, Dmitri

[["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Neuroimmunology"],["dc.bibliographiccitation.volume","253"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Schlaeger, Christian"],["dc.contributor.author","Koerner, Henrike"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger"],["dc.contributor.author","Kitz, Alexandra"],["dc.contributor.author","Nosov, Michail"],["dc.contributor.author","Haberl, Michael"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T09:02:16Z"],["dc.date.available","2018-11-07T09:02:16Z"],["dc.date.issued","2012"],["dc.identifier.isi","000312764800352"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24643"],["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","Direct imaging of T cell activation during experimental autoimmune encephalomyelitis"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","349"],["dc.bibliographiccitation.issue","7590"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","530"],["dc.contributor.author","Schlaeger, Christian"],["dc.contributor.author","Koerner, Henrike"],["dc.contributor.author","Krueger, Martin"],["dc.contributor.author","Vidoli, Stefano"],["dc.contributor.author","Haberl, Michael"],["dc.contributor.author","Mielke, Dorothee"],["dc.contributor.author","Brylla, Elke"],["dc.contributor.author","Issekutz, Thomas B."],["dc.contributor.author","Cabanas, Carlos"],["dc.contributor.author","Nelsons, Peter J."],["dc.contributor.author","Ziemssen, Tjalf"],["dc.contributor.author","Rohde, Veit"],["dc.contributor.author","Bechmann, Ingo"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T10:18:08Z"],["dc.date.available","2018-11-07T10:18:08Z"],["dc.date.issued","2016"],["dc.description.abstract","In multiple sclerosis, brain-reactive T cells invade the central nervous system (CNS) and induce a self-destructive inflammatory process. T-cell infiltrates are not only found within the parenchyma and the meninges, but also in the cerebrospinal fluid (CSF) that bathes the entire CNS tissue(1,2). How the T cells reach the CSF, their functionality, and whether they traffic between the CSF and other CNS compartments remains hypothetical(3-6). Here we show that effector T cells enter the CSF from the leptomeninges during Lewis rat experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. While moving through the three-dimensional leptomeningeal network of collagen fibres in a random Brownian walk, T cells were flushed from the surface by the flow of the CSF. The detached cells displayed significantly lower activation levels compared to T cells from the leptomeninges and CNS parenchyma. However, they did not represent a specialized non-pathogenic cellular sub-fraction, as their gene expression profile strongly resembled that of tissue-derived T cells and they fully retained their encephalitogenic potential. T-cell detachment from the leptomeninges was counteracted by integrins VLA-4 and LFA-1 binding to their respective ligands produced by resident macrophages. Chemokine signalling via CCR5/CXCR3 and antigenic stimulation of T cells in contact with the leptomeningeal macrophages enforced their adhesiveness. T cells floating in the CSF were able to reattach to the leptomeninges through steps reminiscent of vascular adhesion in CNS blood vessels, and invade the parenchyma. The molecular/cellular conditions for T-cell reattachment were the same as the requirements for detachment from the leptomeningeal milieu. Our data indicate that the leptomeninges represent a checkpoint at which activated T cells are licensed to enter the CNS parenchyma and non-activated T cells are preferentially released into the CSF, from where they can reach areas of antigen availability and tissue damage."],["dc.identifier.doi","10.1038/nature16939"],["dc.identifier.isi","000370327100040"],["dc.identifier.pmid","26863192"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-4687"],["dc.relation.issn","0028-0836"],["dc.title","Effector T-cell trafficking between the leptomeninges and the cerebrospinal fluid"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","675"],["dc.bibliographiccitation.issue","7413"],["dc.bibliographiccitation.journal","Nature"],["dc.bibliographiccitation.volume","488"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Sie, Christopher"],["dc.contributor.author","Streyl, Kristina"],["dc.contributor.author","Ulaganathan, Vijay Kumar"],["dc.contributor.author","Schlaeger, Christian"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Heckelsmiller, Klaus"],["dc.contributor.author","Nietfeld, Wilfried"],["dc.contributor.author","Ellwart, Joachim W."],["dc.contributor.author","Klinkert, Wolfgang E. F."],["dc.contributor.author","Lottaz, Claudio"],["dc.contributor.author","Nosov, Mikhail"],["dc.contributor.author","Brinkmann, Volker"],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Lehrach, Hans"],["dc.contributor.author","Vingron, Martin"],["dc.contributor.author","Wekerle, Hartmut"],["dc.contributor.author","Fluegel-Koch, Cassandra"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T09:07:04Z"],["dc.date.available","2018-11-07T09:07:04Z"],["dc.date.issued","2012"],["dc.description.abstract","The blood-brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB1,2 and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma(3-6). Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease."],["dc.identifier.doi","10.1038/nature11337"],["dc.identifier.isi","000308095100060"],["dc.identifier.pmid","22914092"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25704"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0028-0836"],["dc.title","T cells become licensed in the lung to enter the central nervous system"],["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","Odoardi, Francesca"],["dc.contributor.author","Schlaeger, Christian"],["dc.contributor.author","Koerner, Henrike"],["dc.contributor.author","Haberl, Michael"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T09:33:36Z"],["dc.date.available","2018-11-07T09:33:36Z"],["dc.date.issued","2014"],["dc.format.extent","204"],["dc.identifier.doi","10.1016/j.jneuroim.2014.08.548"],["dc.identifier.isi","000345192100537"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32001"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Mainz, GERMANY"],["dc.relation.issn","1872-8421"],["dc.relation.issn","0165-5728"],["dc.title","In vivo visualization of the role of chemokines in migratory T cells during CNS inflammation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1930"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","1943"],["dc.bibliographiccitation.volume","133"],["dc.contributor.author","Cordiglieri, Chiara"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Zhang, B. O."],["dc.contributor.author","Nebel, Merle"],["dc.contributor.author","Kawakami, Naoto"],["dc.contributor.author","Klinkert, Wolfgang E. F."],["dc.contributor.author","Lodygin, Dimtri"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Breunig, Esther"],["dc.contributor.author","Schild, Detlev"],["dc.contributor.author","Ulaganathan, Vijay Kumar"],["dc.contributor.author","Dornmair, Klaus"],["dc.contributor.author","Dammermann, Werner"],["dc.contributor.author","Potter, Barry V. L."],["dc.contributor.author","Guse, Andreas H."],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T08:41:30Z"],["dc.date.available","2018-11-07T08:41:30Z"],["dc.date.issued","2010"],["dc.description.abstract","Nicotinic acid adenine dinucleotide phosphate represents a newly identified second messenger in T cells involved in antigen receptor-mediated calcium signalling. Its function in vivo is, however, unknown due to the lack of biocompatible inhibitors. Using a recently developed inhibitor, we explored the role of nicotinic acid adenine dinucleotide phosphate in autoreactive effector T cells during experimental autoimmune encephalomyelitis, the animal model for multiple sclerosis. We provide in vitro and in vivo evidence that calcium signalling controlled by nicotinic acid adenine dinucleotide phosphate is relevant for the pathogenic potential of autoimmune effector T cells. Live two photon imaging and molecular analyses revealed that nicotinic acid adenine dinucleotide phosphate signalling regulates T cell motility and re-activation upon arrival in the nervous tissues. Treatment with the nicotinic acid adenine dinucleotide phosphate inhibitor significantly reduced both the number of stable arrests of effector T cells and their invasive capacity. The levels of pro-inflammatory cytokines interferon-gamma and interleukin-17 were strongly diminished. Consecutively, the clinical symptoms of experimental autoimmune encephalomyelitis were ameliorated. In vitro, antigen-triggered T cell proliferation and cytokine production were evenly suppressed. These inhibitory effects were reversible: after wash-out of the nicotinic acid adenine dinucleotide phosphate antagonist, the effector T cells fully regained their functions. The nicotinic acid derivative BZ194 induced this transient state of non-responsiveness specifically in post-activated effector T cells. Naive and long-lived memory T cells, which express lower levels of the putative nicotinic acid adenine dinucleotide phosphate receptor, type 1 ryanodine receptor, were not targeted. T cell priming and recall responses in vivo were not reduced. These data indicate that the nicotinic acid adenine dinucleotide phosphate/calcium signalling pathway is essential for the recruitment and the activation of autoaggressive effector T cells within their target organ. Interference with this signalling pathway suppresses the formation of autoimmune inflammatory lesions and thus might qualify as a novel strategy for the treatment of T cell mediated autoimmune diseases."],["dc.identifier.doi","10.1093/brain/awq135"],["dc.identifier.isi","000279473900008"],["dc.identifier.pmid","20519328"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6202"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19486"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","0006-8950"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Nicotinic acid adenine dinucleotide phosphate-mediated calcium signalling in effector T cells regulates autoimmunity of the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","60"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","69"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Kebir, Hania"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Litke, Tanja"],["dc.contributor.author","Sonneck, Maike"],["dc.contributor.author","Alvarez, Jorge Ivan"],["dc.contributor.author","Winchenbach, Jan"],["dc.contributor.author","Eckert, Nadine"],["dc.contributor.author","Hayardeny, Liat"],["dc.contributor.author","Sorani, Ella"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Prat, Alexandre"],["dc.date.accessioned","2018-11-07T10:23:36Z"],["dc.date.available","2018-11-07T10:23:36Z"],["dc.date.issued","2017"],["dc.description.abstract","Laquinimod is currently being tested as a therapeutic drug in multiple sclerosis. However, its exact mechanism of action is still under investigation. Tracking of fluorescently-tagged encephalitogenic T cells during experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, revealed that laquinimod significantly reduces the invasion of pathogenic effector T cells into the CNS tissue. T-cell activation, differentiation and amplification within secondary lymphoid organs after immunization with myelin antigen, their migratory capacity and re-activation within the nervous tissue were either only mildly affected or remained unchanged. Instead, laquinimod directly impacted the functionality of the CNS vasculature. The expression of tight junction proteins p120 and ZO-1 in human brain endothelial cells was up-regulated upon laquinimod treatment, resulting in a significant increase in the transendothelial electrical resistance of confluent monolayers of brain endothelial cells. Similarly, expression of the adhesion molecule activated leukocyte cell adhesion molecule (ALCAM) and inflammatory chemokines CCL2 and IP-10 was suppressed, leading to a significant reduction in the migration of memory T(H)1 and T(H)17 lymphocytes across the blood brain barrier (BBB). Our data indicate that laquinimod exerts its therapeutic effects by tightening the BBB and limiting parenchymal invasion of effector T cells, thereby reducing CNS damage. (C) 2017 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2017.02.002"],["dc.identifier.isi","000399262300006"],["dc.identifier.pmid","28235673"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42494"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1095-953X"],["dc.relation.issn","0969-9961"],["dc.title","Laquinimod enhances central nervous system barrier functions"],["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","253"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Sie, Christopher"],["dc.contributor.author","Schlaeger, Christian"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Fluegel-Koch, Cassandra"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T09:02:17Z"],["dc.date.available","2018-11-07T09:02:17Z"],["dc.date.issued","2012"],["dc.format.extent","131"],["dc.identifier.isi","000312764800351"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24644"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.publisher.place","Amsterdam"],["dc.relation.eventlocation","Boston, MA"],["dc.relation.issn","0165-5728"],["dc.title","T cell invasion of the CNS: the lung paths the way"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","784"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Lodygin, Dmitri"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Schlaeger, Christian"],["dc.contributor.author","Koerner, Henrike"],["dc.contributor.author","Kitz, Alexandra"],["dc.contributor.author","Nosov, Michail"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Haberl, Michael"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T09:24:11Z"],["dc.date.available","2018-11-07T09:24:11Z"],["dc.date.issued","2013"],["dc.description.abstract","Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluorescently labeled nuclear factor of activated T cells (NFAT) with histone protein H2B to create a broadly applicable molecular sensor for intravital imaging of T cell activation. In experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, we report that effector T cells entering the CNS become activated after short contacts with leptomeningeal phagocytes. During established disease, the activation process is extended to the depth of the CNS parenchyma, where the cells form contacts with microglia and recruited phagocytes. We show that it is the activation processes during the preclinical phase rather than during established disease that are essential for the intensity and duration of the disease bout."],["dc.identifier.doi","10.1038/nm.3182"],["dc.identifier.isi","000319981600030"],["dc.identifier.pmid","23624600"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29760"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.title","A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]