NFATc1 controls the activity of CD8+T lymphocytes at multiple levels
- Speaker: Professor Edgar Serfling, Department of Molecular Pathology, Institute of Pathology, University of Wuerzburg, Germany.
In the nuclei of activated lymphocytes, NFATc1 is the most prominent NFAT transcription factor. By studying cytotoxic T cells (CTLs) deficient for NFATc1 we showed that NFATc1 controls the cytotoxicity of murine CTLs. Activation of Nfatc1-/- CTLs revealed alterations in their cytoskeleton re-organisation and recruitment of cytosolic organelles to immunological synapse. They exhibited an impaired cytotoxicity against tumour cells, and mice bearing Nfatc1-/- T cells showed a retarded clearing of Listeria bacteria upon infection. Transcriptome analysis revealed diminished RNA levels of numerous genes in Nfatc1-/- CD8+T cells. Among them are the Tbx21, GzmB and numerous genes encoding cytokines and chemokines, and almost all genes controlling aerobic glycolysis. Nfatc1-/- but not Nfatc2-/- CD8+T cells revealed an impaired metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis which could be restored by adding IL-2. Genome-wide ChIP seq assays demonstrated NFATc1 binding to many genes controlling CTL activity. These data indicate NFATc1 as a key factor controlling the effector functions of CTLs.
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