Litke, Tanja

[["dc.bibliographiccitation.firstpage","1326"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","1338"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Lee, De-Hyung"],["dc.contributor.author","Flach, Anne-Christine"],["dc.contributor.author","Litke, Tanja"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Lingner, Thomas"],["dc.contributor.author","Bommhardt, Ursula"],["dc.contributor.author","Sendtner, Michael"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Fluegel, Alexander"],["dc.contributor.author","Luehder, Fred"],["dc.date.accessioned","2018-11-07T09:57:51Z"],["dc.date.available","2018-11-07T09:57:51Z"],["dc.date.issued","2015"],["dc.description.abstract","Brain-derived neurotrophic factor (BDNF) promotes neuronal survival, regeneration, and plasticity. Emerging evidence also indicates an essential role for BDNF outside the nervous system, for instance in immune cells. We therefore investigated the impact of BDNF on Tcells using BDNF knockout (KO) mice and conditional KO mice lacking BDNF specifically in this lymphoid subset. In both settings, we observed diminished T-cell cellularity in peripheral lymphoid organs and an increase in CD4(+)CD44(+) memory Tcells. Analysis of thymocyte development revealed diminished total thymocyte numbers, accompanied by a significant increase in CD4/CD8 double-negative (DN) thymocytes due to a partial block in the transition from the DN3 to the DN4 stage. This was neither due to increased thymocyte apoptosis nor defects in the expression of the TCR- chain or the pre-TCR. In contrast, pERK but not pAKT levels were diminished in DN3 BDNF-deficient thymocytes. BDNF deficiency in Tcells did not result in gross deficits in peripheral acute immune responses nor in changes of the homeostatic proliferation of peripheral Tcells. Taken together, our data reveal a critical autocrine and/or paracrine role of T-cell-derived BDNF in thymocyte maturation involving ERK-mediated TCR signaling pathways."],["dc.identifier.doi","10.1002/eji.201444985"],["dc.identifier.isi","000354182300006"],["dc.identifier.pmid","25627579"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37248"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","Thymocyte-derived BDNF influences T-cell maturation at the DN3/DN4 transition stage"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3323"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","3328"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Flach, Anne-Christine"],["dc.contributor.author","Litke, Tanja"],["dc.contributor.author","Strauss, Judith"],["dc.contributor.author","Haberl, Michael"],["dc.contributor.author","Gomez, Cesar Cordero"],["dc.contributor.author","Reindl, Markus"],["dc.contributor.author","Saiz, Albert"],["dc.contributor.author","Fehling, Hans-Joerg"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Fluegel, Alexander"],["dc.date.accessioned","2018-11-07T10:16:44Z"],["dc.date.available","2018-11-07T10:16:44Z"],["dc.date.issued","2016"],["dc.description.abstract","Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue."],["dc.identifier.doi","10.1073/pnas.1519608113"],["dc.identifier.isi","000372488200061"],["dc.identifier.pmid","26957602"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41093"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease"],["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"]]