TY - THES A1 - Lischke, Timo T1 - Functional correlates of CD4+ cell tolerance and immunity to soluble protein antigen in vivo Y1 - 2009 SN - 978-3-89432-116-1 PB - Westarp Wissenschaften CY - Hohenwarsleben ER - TY - JOUR A1 - Kobel-Höller, Konstanze A1 - Gley, Kevin A1 - Jochinke, Janina A1 - Heider, Kristina A1 - Fritsch, Verena Nadin A1 - Ha Viet Duc Nguyen, A1 - Lischke, Timo A1 - Radek, Renate A1 - Baumgrass, Ria A1 - Mutzel, Rupert A1 - Thewes, Sascha T1 - Calcineurin Silencing in Dictyostelium discoideum Leads to Cellular Alterations Affecting Mitochondria, Gene Expression, and Oxidative Stress Response JF - Protist N2 - Calcineurin is involved in development and cell differentiation of the social amoeba Dictyostelium discoideum. However, since knockouts of the calcineurin-encoding genes are not possible in D. discoideum it is assumed that the phosphatase also plays a crucial role during vegetative growth of the amoebae. Therefore, we investigated the role of calcineurin during vegetative growth in D. discoideum. RNAi-silenced calcineurin mutants showed cellular alterations with an abnormal morphology of mitochondria and had increased content of mitochondrial DNA (mtDNA). In contrast, mitochondria showed no substantial functional impairment. Calcineurin-silencing led to altered expression of calcium-regulated genes as well as mitochondrially-encoded genes. Furthermore, genes related to oxidative stress were higher expressed in the mutants, which correlated to an increased resistance towards reactive oxygen species (ROS). Most of the changes observed during vegetative growth were not seen after starvation of the calcineurin mutants. We show that impairment of calcineurin led to many subtle, but in the sum crucial cellular alterations in vegetative D. discoideum cells. As these alterations were not observed after starvation we propose a dual role for calcineurin during growth and development. Our results imply that calcineurin is one player in the mutual interplay between mitochondria and ROS during vegetative growth. KW - mtDNA KW - mitochondrial remodelling KW - calcium KW - oxidative stress KW - phototaxis Y1 - 2018 U6 - https://doi.org/10.1016/j.protis.2018.04.004 SN - 1434-4610 VL - 169 IS - 4 SP - 584 EP - 602 PB - Elsevier GMBH CY - München ER - TY - JOUR A1 - Gryzik, Stefanie A1 - Hoang, Yen A1 - Lischke, Timo A1 - Mohr, Elodie A1 - Venzke, Melanie A1 - Kadner, Isabelle A1 - Pötzsch, Josephine A1 - Groth, Detlef A1 - Radbruch, Andreas A1 - Hutloff, Andreas A1 - Baumgrass, Ria T1 - Identification of a super-functional Tfh-like subpopulation in murine lupus by pattern perception JF - eLife N2 - Dysregulated cytokine expression by T cells plays a pivotal role in the pathogenesis of autoimmune diseases. However, the identification of the corresponding pathogenic subpopulations is a challenge, since a distinction between physiological variation and a new quality in the expression of protein markers requires combinatorial evaluation. Here, we were able to identify a super-functional follicular helper T cell (Tfh)-like subpopulation in lupus-prone NZBxW mice with our binning approach "pattern recognition of immune cells (PRI)". PRI uncovered a subpopulation of IL-21(+) IFN-gamma(high) PD-1(low) CD40L(high) CXCR5(-) Bcl-6(-) T cells specifically expanded in diseased mice. In addition, these cells express high levels of TNF-alpha and IL-2, and provide B cell help for IgG production in an IL-21 and CD40L dependent manner. This super-functional T cell subset might be a superior driver of autoimmune processes due to a polyfunctional and high cytokine expression combined with Tfh-like properties. Y1 - 2020 U6 - https://doi.org/10.7554/eLife.53226 SN - 2050-084X VL - 9 PB - eLife Sciences Publications CY - Cambridge ER -