@article{BaurOttoStegeretal.2018,
  author    = {Baur, Johannes and Otto, Christoph and Steger, Ulrich and Klein-Hessling, Stefan and Muhammad, Khalid and Pusch, Tobias and Murti, Krisna and Wismer, Rhoda and Germer, Christoph-Thomas and Klein, Ingo and M{\"u}ller, Nora and Serfling, Edgar and Avots, Andris},
  title     = {The transcription factor NFaTc1 supports the rejection of heterotopic heart allografts},
  series = {Frontiers in Immunology},
  volume    = {9},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2018.01338},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221530},
  year      = {2018},
  abstract  = {The immune suppressants cyclosporin A (CsA) and tacrolimus (FK506) are used worldwide in transplantation medicine to suppress graft rejection. Both CsA and FK506 inhibit the phosphatase calcineurin (CN) whose activity controls the immune receptor-mediated activation of lymphocytes. Downstream targets of CN in lymphocytes are the nuclear factors of activated T cells (NFATs). We show here that the activity of NFATc1, the most prominent NFAT factor in activated lymphocytes supports the acute rejection of heterotopic heart allografts. While ablation of NFATc1 in T cells prevented graft rejection, ectopic expression of inducible NFATc1/αA isoform led to rejection of heart allografts in recipient mice. Acceptance of transplanted hearts in mice bearing NFATc1-deficient T cells was accompanied by a reduction in number and cytotoxicity of graft infiltrating cells. In CD8\(^+\) T cells, NFATc1 controls numerous intracellular signaling pathways that lead to the metabolic switch to aerobic glycolysis and the expression of numerous lymphokines, chemokines, and their receptors, including Cxcr3 that supports the rejection of allogeneic heart transplants. These findings favors NFATc1 as a molecular target for the development of new strategies to control the cytotoxicity of T cells upon organ transplantation.},
  language  = {en}
}
@article{KleinHesslingMuhammadKleinetal.2017,
  author    = {Klein-Hessling, Stefan and Muhammad, Khalid and Klein, Matthias and Pusch, Tobias and Rudolf, Ronald and Fl{\"o}ter, Jessica and Qureischi, Musga and Beilhack, Andreas and Vaeth, Martin and Kummerow, Carsten and Backes, Christian and Schoppmeyer, Rouven and Hahn, Ulrike and Hoth, Markus and Bopp, Tobias and Berberich-Siebelt, Friederike and Patra, Amiya and Avots, Andris and M{\"u}ller, Nora and Schulze, Almut and Serfling, Edgar},
  title     = {NFATc1 controls the cytotoxicity of CD8\(^{+}\) T cells},
  series = {Nature Communications},
  volume    = {8},
  journal   = {Nature Communications},
  number    = {511},
  doi       = {10.1038/s41467-017-00612-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170353},
  year      = {2017},
  abstract  = {Cytotoxic T lymphocytes are effector CD8\(^{+}\) T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1\(^{-/-}\) cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection. Transcriptome analysis shows diminished RNA levels of numerous genes in Nfatc1\(^{-/-}\) CD8\(^{+}\) T cells, including Tbx21, Gzmb and genes encoding cytokines and chemokines, and genes controlling glycolysis. Nfatc1\(^{-/-}\), but not Nfatc2\(^{-/-}\) CD8\(^{+}\) T cells have an impaired metabolic switch to glycolysis, which can be restored by IL-2. Genome-wide ChIP-seq shows that NFATc1 binds many genes that control cytotoxic T lymphocyte activity. Together these data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.},
  language  = {en}
}