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 - TY - JOUR A1 - Jargosch, M. A1 - Kroeger, S. A1 - Gralinska, E. A1 - Klotz, Ulrike A1 - Fang, Z. A1 - Chen, W. A1 - Leser, U. A1 - Selbig, Joachim A1 - Groth, Detlef A1 - Baumgrass, Ria T1 - Data integration for identification of important transcription factors of STAT6-mediated cell fate decisions JF - Genetics and molecular research N2 - Data integration has become a useful strategy for uncovering new insights into complex biological networks. We studied whether this approach can help to delineate the signal transducer and activator of transcription 6 (STAT6)-mediated transcriptional network driving T helper (Th) 2 cell fate decisions. To this end, we performed an integrative analysis of publicly available RNA-seq data of Stat6-knockout mouse studies together with STAT6 ChIP-seq data and our own gene expression time series data during Th2 cell differentiation. We focused on transcription factors (TFs), cytokines, and cytokine receptors and delineated 59 positively and 41 negatively STAT6-regulated genes, which were used to construct a transcriptional network around STAT6. The network illustrates that important and well-known TFs for Th2 cell differentiation are positively regulated by STAT6 and act either as activators for Th2 cells (e.g., Gata3, Atf3, Satb1, Nfil3, Maf, and Pparg) or as suppressors for other Th cell subpopulations such as Th1 (e.g., Ar), Th17 (e.g., Etv6), or iTreg (e.g., Stat3 and Hifla) cells. Moreover, our approach reveals 11 TFs (e.g., Atf5, Creb3l2, and Asb2) with unknown functions in Th cell differentiation. This fact together with the observed enrichment of asthma risk genes among those regulated by STAT6 underlines the potential value of the data integration strategy used here. Thus, our results clearly support the opinion that data integration is a useful tool to delineate complex physiological processes. KW - Data integration KW - Th2 cells KW - Gene regulatory network KW - STAT6 KW - Transcription factors Y1 - 2016 U6 - https://doi.org/10.4238/gmr.15028493 SN - 1676-5680 VL - 15 PB - FUNPEC CY - Ribeirao Preto 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 -