NFATc1 controls the cytotoxicity of CD8+ T cells

Stefan Klein-Hessling, Khalid Muhammad, Matthias Klein, Tobias Pusch, Ronald Rudolf, Jessica Flöter, Musga Qureischi, Andreas Beilhack, Martin Vaeth, Carsten Kummerow, Christian Backes, Rouven Schoppmeyer, Ulrike Hahn, Markus Hoth, Tobias Bopp, Friederike Berberich-Siebelt, Amiya Patra, Andris Avots, Nora Müller, Almut Schulze and Edgar Serfling ()
Additional contact information
Stefan Klein-Hessling: University of Würzburg
Khalid Muhammad: University of Würzburg
Matthias Klein: University of Mainz
Tobias Pusch: University of Würzburg
Ronald Rudolf: University of Würzburg
Jessica Flöter: University of Würzburg
Musga Qureischi: University Würzburg
Andreas Beilhack: University Würzburg
Martin Vaeth: University of Würzburg
Carsten Kummerow: Saarland University
Christian Backes: Saarland University
Rouven Schoppmeyer: Saarland University
Ulrike Hahn: Saarland University
Markus Hoth: Saarland University
Tobias Bopp: University of Mainz
Friederike Berberich-Siebelt: University of Würzburg
Amiya Patra: University of Würzburg
Andris Avots: University of Würzburg
Nora Müller: University of Würzburg
Almut Schulze: University of Würzburg
Edgar Serfling: University of Würzburg

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00612-6

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DOI: 10.1038/s41467-017-00612-6

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