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 SchulzeEdgar Serfling

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)

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.

Original languageEnglish
Article number511
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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