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.

中文翻译：

---

NFATc1控制CD8 + T细胞的细胞毒性。

细胞毒性T淋巴细胞是效应CD8 ⁺ T细胞，可消除感染的细胞和恶性细胞。在这里，我们显示了转录因子NFATc1控制着小鼠细胞毒性T淋巴细胞的细胞毒性。Nfatc1 ^-/-细胞毒性T淋巴细胞的激活显示出细胞骨架组织的缺陷和胞浆细胞器募集到免疫突触。这些细胞对肿瘤细胞的细胞毒性降低，具有NFATc1缺陷T细胞的小鼠在控制李斯特菌感染方面存在缺陷。转录组分析显示Nfatc1 ^-/- CD8 ⁺ T细胞中许多基因的RNA水平降低，包括Tbx21，Gzmb和编码细胞因子和趋化因子的基因，以及控制糖酵解的基因。Nfatc1 ^-/-，但Nfatc2 ^-/- CD8 ⁺ T细胞没有发生向糖酵解的新陈代谢转换受损的现象，可以通过IL-2恢复。全基因组ChIP-seq显示NFATc1结合了许多控制细胞毒性T淋巴细胞活性的基因。这些数据一起表明NFATc1是细胞毒性T淋巴细胞效应子功能的重要调节剂。已证明NFAT核易位是响应病毒感染产生CD8 ⁺ T细胞细胞因子所必需的。在这里，作者表明NFATc1控制着对细菌和肿瘤细胞最佳反应所需的活化CD8 ⁺ T细胞的细胞毒性和新陈代谢转换。