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.NFAT nuclear translocation has been shown to be required for CD8+ T cell cytokine production in response to viral infection. Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Nature communications - 8(2017), 1 vom: 11. Sept., Seite 511 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Klein-Hessling, Stefan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.01.2018 Date Revised 13.11.2018 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-017-00612-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM275651185 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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.NFAT nuclear translocation has been shown to be required for CD8+ T cell cytokine production in response to viral infection. Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells | ||
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| 700 | 1 | |a Muhammad, Khalid |e verfasserin |4 aut | |
| 700 | 1 | |a Klein, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Pusch, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Rudolf, Ronald |e verfasserin |4 aut | |
| 700 | 1 | |a Flöter, Jessica |e verfasserin |4 aut | |
| 700 | 1 | |a Qureischi, Musga |e verfasserin |4 aut | |
| 700 | 1 | |a Beilhack, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Vaeth, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Kummerow, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Backes, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Schoppmeyer, Rouven |e verfasserin |4 aut | |
| 700 | 1 | |a Hahn, Ulrike |e verfasserin |4 aut | |
| 700 | 1 | |a Hoth, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Bopp, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Berberich-Siebelt, Friederike |e verfasserin |4 aut | |
| 700 | 1 | |a Patra, Amiya |e verfasserin |4 aut | |
| 700 | 1 | |a Avots, Andris |e verfasserin |4 aut | |
| 700 | 1 | |a Müller, Nora |e verfasserin |4 aut | |
| 700 | 1 | |a Schulze, Almut |e verfasserin |4 aut | |
| 700 | 1 | |a Serfling, Edgar |e verfasserin |4 aut | |
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