Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-17035 Wissenschaftlicher Artikel Klein-Hessling, Stefan; Muhammad, Khalid; Klein, Matthias; Pusch, Tobias; Rudolf, Ronald; Flöter, Jessica; Qureischi, Musga; Beilhack, Andreas; Vaeth, Martin; Kummerow, Carsten; Backes, Christian; Schoppmeyer, Rouven; Hahn, Ulrike; Hoth, Markus; Bopp, Tobias; Berberich-Siebelt, Friederike; Patra, Amiya; Avots, Andris; Müller, Nora; Schulze, Almut; Serfling, Edgar NFATc1 controls the cytotoxicity of CD8\(^{+}\) T cells 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. 2017 Nature Communications 8 511 urn:nbn:de:bvb:20-opus-170353 10.1038/s41467-017-00612-6 Pathologisches Institut