Witte, Ann-Kathrin

[["dc.bibliographiccitation.firstpage","1724"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","1732"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Witte, Ann-Kathrin"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Groene, Hermann-Josef"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:15:09Z"],["dc.date.available","2018-11-07T10:15:09Z"],["dc.date.issued","2016"],["dc.description.abstract","T-cell lymphopenia is a major risk factor for autoimmunity. Here we describe congenic Lewis (LEW) rats with a loss-of-function mutation in the Gimap5 gene, leading to a 92% reduction in peripheral T-cell numbers. Gimap5-deficient LEW rats developed eosinophilic autoimmune gastroenteritis accompanied by a 40-fold increase in IgE serum levels. This phenotype was ameliorated by antibiotic treatment, indicating a critical role of the microbial flora in the development of inflammatory bowel disease. Interestingly, Gimap5-deficient LEW rats showed strongly aggravated experimental autoimmune encephalomyelitis (EAE) after immunization with guinea pig myelin basic protein. This phenotype, however, persisted after antibiosis, confirming that the enhanced CNS autoimmune response in T-cell lymphopenic Gimap5-deficient LEW rats was unrelated to the composition of the microbial flora. Rather, it seems that it was caused by the 7-fold increase in the percentage of activated T cells producing IL-17 and IFN-gamma, and the skewed T-cell receptor (TCR) repertoire, both of which were the result of T-cell lymphopenia and not affected by antibiosis. This notion was supported by the observation that adoptive T-cell transfer corrected the TCR repertoire and improved EAE. Collectively, our findings confirm a critical albeit differential role of T-cell lymphopenia in the susceptibility to organ-specific autoimmune responses.-Fischer, H.J., Witte, A.-K., Walter, L., Grone, H.-J., van den Brandt, J., Reichardt, H.M. Distinct roles of T-cell lymphopenia and the microbial flora for gastrointestinal and CNS autoimmunity."],["dc.identifier.doi","10.1096/fj.15-277384"],["dc.identifier.isi","000374879400004"],["dc.identifier.pmid","26740263"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40753"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","1530-6860"],["dc.relation.issn","0892-6638"],["dc.title","Distinct roles of T-cell lymphopenia and the microbial flora for gastrointestinal and CNS autoimmunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1910"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The Journal of Immunology"],["dc.bibliographiccitation.lastpage","1920"],["dc.bibliographiccitation.volume","198"],["dc.contributor.author","Fischer, Henrike J."],["dc.contributor.author","Sie, Christopher"],["dc.contributor.author","Schumann, Eric"],["dc.contributor.author","Witte, Ann-Kathrin"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.date.accessioned","2018-11-07T10:27:04Z"],["dc.date.available","2018-11-07T10:27:04Z"],["dc.date.issued","2017"],["dc.description.abstract","T cell activation is an energy-demanding process fueled by increased glucose consumption and accompanied by upregulation of the insulin receptor (INSR). In this article, we report that silencing the INSR in inducible knockdown rats impairs selective T cell functions but not thymocyte development. Glucose transport and glycolysis in activated CD4(+) T cells were compromised in the absence of the INSR, which was associated with alterations in intracellular signaling pathways. The observed metabolic defects coincided with reduced cytokine production, proliferation, and migration, as well as increased apoptosis of CD4(+) T cells. The cytotoxicity of CD8(+) T cells in response to alloantigens was also diminished under these conditions, whereas the frequency and suppressive capacity of regulatory T cells were unaffected. The observed impairments proved to be decisive in vivo because silencing of the INSR attenuated clinical symptoms in animal models of acute graft-versus-host disease and multiple sclerosis. Taken together, our results suggest that upregulation of the INSR on T cells following activation is required for efficient adaptive immunity."],["dc.identifier.doi","10.4049/jimmunol.1601011"],["dc.identifier.isi","000395904000017"],["dc.identifier.pmid","28115529"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43175"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Assoc Immunologists"],["dc.relation.issn","1550-6606"],["dc.relation.issn","0022-1767"],["dc.title","The Insulin Receptor Plays a Critical Role in T Cell Function and Adaptive Immunity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]