NFAT2 Regulates Generation of Innate-Like CD8+ T Lymphocytes and CD8+ T Lymphocytes Responses

Pachulec, Emilia; Neitzke-Montinelli, Vanessa; Viola, João P. B.

doi:10.3389/fimmu.2016.00411

Cited by 13 publications

(14 citation statements)

References 65 publications

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“…after thymic selection 30 . Taken together, our NGS and ChIP seq data on the genome-wide gene control by NFATc1 in CD8 + T cells confirm and extend the data by Pachulec et al 11 on the NFATc1-mediated control of IFNγ production in CD8 + T cells.…”

Section: Discussionsupporting

confidence: 90%

“…The latter showed a decrease in their cytotoxicity (Supplementary Fig. 3 a), similar to the findings published by Pachulec et al 11 for Nfatc1 −/− CD8 + T cells.…”

Section: Discussionsupporting

confidence: 90%

“…In a study on the ablation of NFATc1 (NFAT2) in murine CD8 + T cells, Pachulec et al 11 described an increase in the percentage of CD8 + CD44 high CD122 + cells in thymus, spleen and LNs of unchallenged Nfatc1 f/f x CD4-cre mice which the authors classified as innate-like CD8 + T cells with characteristics of conventional memory CD8 + T cells. In our Listeria infection assays, we observed a slight increase in the number of Nfatc1 −/− T CM , compared to WT cells, and a decrease of Nfatc1 −/− T EM cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In one study, a defective nuclear translocation of NFATc1 has been described for NFATc1 in CD8 + T cells upon chronic infection 9 , whereas in another study a predominant nuclear localization of NFATc1 was reported for anergic CD8 + T cells 10 . The effect of NFATc1 (NFAT2) ablation on CD8 + T cell physiology has been reported 11 , but genome-wide assays on the effect of NFATc1 on gene expression in CTLs have not.…”

Section: Introductionmentioning

confidence: 99%

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NFATc1 controls the cytotoxicity of CD8+ T cells

et al. 2017

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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.

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Section: Discussionsupporting

confidence: 90%

“…The latter showed a decrease in their cytotoxicity (Supplementary Fig. 3 a), similar to the findings published by Pachulec et al 11 for Nfatc1 −/− CD8 + T cells.…”

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NFATc1 controls the cytotoxicity of CD8+ T cells

et al. 2017

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“…NFAT is a transcription factor that is predominantly regulated by activation and the subsequent translocation from the cytoplasm to the nucleus. NFAT activation/regulation is measured by total NFAT2 protein/mRNA expression levels (45,46). The results demonstrated that the ARB VAL attenuated the HG-induced increase of TRPC6 and NFAT in podocytes in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 95%

Participation of the AngII/TRPC6/NFAT axis in the pathogenesis of podocyte injury in rats with type 2 diabetes

Zhou

et al. 2019

Mol Med Report

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The canonical transient receptor potential channel 6 ion channel is expressed in podocytes and is an important component of the glomerular slit diaphragm. Focal segmental glomerulosclerosis is closely associated with TRPC6 gene mutations, and TRPC6 mediates podocyte injury induced by high glucose. Angiotensin II (AngII) has been revealed to enhance TRPC6 currents in certain types of cells, including podocytes and ventricular myocytes. It has been reported that glucose regulated TRPC6 expression in an AngII-dependent manner in podocytes and that this pathway is critical in diabetic nephropathy. In the present study, the role of TRPC6 detected by western blotting and reverse transcription-quantitative polymerase chain reaction in AngII-mediated podocyte injury was evaluated in rats with type 2 diabetes induced by high-calorie diets and streptozotocin. The results demonstrated that urinary albumin excretion was elevated, and morphological changes, including glomerular basement membrane thickening and podocyte process effacement, were observed. There was increased expression of AngII and TRPC6 in diabetic rats. The angiotensin receptor blocker valsartan significantly reduced TRPC6 and nuclear factor of activated T-cells (NFAT) overexpression in diabetic rats. These results in vivo were confirmed by studies in vitro, which demonstrated that inhibition of TRPC6 ameliorated high glucose-induced podocyte injury by decreasing NFAT mRNA levels. Taken together, the present results suggested that the AngII/TRPC6/NFAT axis may be a crucial signaling pathway in podocytes that is necessary for maintaining the integrity of the glomerular filtration barrier. In addition, TRPC6 may represent a potential therapeutic target for diabetic nephropathy.

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Differential interferon-γ production by naive and memory-like CD8 T cells

Araújo-Souza

Hanschke

Nardy

et al. 2020

Journal of Leukocyte Biology

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CD8 T cells play a crucial role in immune responses to virus infections and tumors. Naïve CD8 T lymphocytes after TCR stimulation undergo differentiation into CTLs and memory cells, which are essential sources of IFN-. We investigated IFN-production by CD8 T cell subsets found in nonimmune mice. A minor fraction of in vitro TCR-stimulated CD8 T cells produce IFN-, and it is regulated at the transcriptional level. Antigen inexperienced C57BL/6 mice present the coexistence of 2 populations. The main population exhibits a CD44 low CD122 low profile, which is compatible with naïve lymphocytes. The minor expresses a phenotype of immunologic memory, CD44 hi CD122 hi. Both subsets are able to produce IL-2 in response to TCR activation, but only the memory-like population is responsible for IFN-production. Similar to memory CD8 T cells, CD44 hi CD8 + T cells also present a higher level of the transcriptional factor Eomes and a lower level of T-bet (Tbx21) mRNA than CD44 low CD8 + T cells. The presence of the CD44 hi CD8 + T cell population in nonimmune OT-I transgenic mice reveals that the population is generated independently of antigenic stimulation. CpG methylation is an efficient epigenetic mechanism for gene silencing. DNA methylation at posttranscriptional CpG sites in the Ifng promoter is higher in CD44 low CD8 + T cells than in CD44 hi CD8 + T cells. Thus, memory-like CD8 T cells have a distinct epigenetic pattern in the Ifng promoter and can rapidly produce IFN-in response to TCR stimulation.

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NFAT2 Regulates Generation of Innate-Like CD8+ T Lymphocytes and CD8+ T Lymphocytes Responses

Cited by 13 publications

References 65 publications

NFATc1 controls the cytotoxicity of CD8+ T cells

NFATc1 controls the cytotoxicity of CD8+ T cells

Participation of the AngII/TRPC6/NFAT axis in the pathogenesis of podocyte injury in rats with type 2 diabetes

Differential interferon-γ production by naive and memory-like CD8 T cells

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