Targets of EOMES in mouse CD4+ T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA606190 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11071282_1.fastq.gz | Fastqsanger.gz | |||
| SRR11071282_2.fastq.gz | Fastqsanger.gz | |||
| SRR11071283_1.fastq.gz | Fastqsanger.gz | |||
| SRR11071283_2.fastq.gz | Fastqsanger.gz | |||
| SRR11071284_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:To gain mechanistic insights into how EOMES regulates CD4+ T-cell differentiation and function, we performed an RNA-seq analysis using Eomes-GFP reporter mice (Eomes+/GFP) to isolate GFP+ (EOMES+) and GFP- (EOMES-) CD4+ T-cells by FACS sorting. We also sequenced RNA from Eomes-deficient GFP+ and GFP- CD4+ T-cells isolated from EomesΔT/GFP knock-out mice, in which one Eomes allele is disrupted by GFP insertion and the DNA-binding domain of the other allele is deleted in T cells by Lck-driven Cre recombinase. Hence, we had two populations of GFP+ cells where the EOMES locus was transcribed, one with a transcriptionally active EOMES protein (Eomes+/GFP) and another one with no transcriptionally active EOMES (EomesΔT/GFP), plus the respective GFP-negative controls isolated from the same mice. A homogeneous population of EOMES-expressing CD4+ T cells were obtained by transferring naïve sorted CD25- CD45RBhigh CD4+ T-cells isolated from Eomes+/GFP reporter or EomesΔT/GFP knock-out donor animals into Rag2-/- mice. After three weeks of adoptive transfer GFP+ and GFP- CD4+ T-cell populations from these mice were FACS-sorted for transcriptome analysis by RNA sequencing.
2020-10-01 | GSE145145 | GEO
Project description:The tissue accumulation of T cells expressing the transcription factor Eomesodermin (Eomes) has been reported in several chronic inflammatory diseases, including multiple sclerosis. However, the mechanisms whereby Eomes controls this accumulation and strengthens inflammation remains ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. We demonstrate that Eomes is dispensable for the initial priming of CD4+ T cells but is required for long-term maintenance of CNS-infiltrating CD4+ T cells. Our transcriptomic studies reveal that the impact Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and function. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in both healthy donors and multiple sclerosis patients. CD4+ T cells expressing Eomes exhibit enhanced mitochondrial functions, which resulted in their increased capacity to survive upon prolonged in vitro stimulation. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.
2023-12-23 | GSE247860 | GEO
Project description:The tissue accumulation of T cells expressing the transcription factor Eomesodermin (Eomes) has been reported in several chronic inflammatory diseases, including multiple sclerosis. However, the mechanisms whereby Eomes controls this accumulation and strengthens inflammation remains ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. We demonstrate that Eomes is dispensable for the initial priming of CD4+ T cells but is required for long-term maintenance of CNS-infiltrating CD4+ T cells. Our transcriptomic studies reveal that the impact Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and function. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in both healthy donors and multiple sclerosis patients. CD4+ T cells expressing Eomes exhibit enhanced mitochondrial functions, which resulted in their increased capacity to survive upon prolonged in vitro stimulation. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.
2023-12-23 | GSE247861 | GEO
Project description:The tissue accumulation of T cells expressing the transcription factor Eomesodermin (Eomes) has been reported in several chronic inflammatory diseases, including multiple sclerosis. However, the mechanisms whereby Eomes controls this accumulation and strengthens inflammation remains ill-defined. Here, we show that Eomes deletion in antigen-specific CD4+ T cells is sufficient to protect against central nervous system (CNS) inflammation. We demonstrate that Eomes is dispensable for the initial priming of CD4+ T cells but is required for long-term maintenance of CNS-infiltrating CD4+ T cells. Our transcriptomic studies reveal that the impact Eomes on effector CD4+ T cell longevity is associated with sustained expression of multiple genes involved in mitochondrial organization and function. Accordingly, epigenetic studies demonstrate that Eomes supports mitochondrial function by direct binding to either metabolism-associated genes or mitochondrial transcriptional modulators. Besides, the significance of these findings was confirmed in both healthy donors and multiple sclerosis patients. CD4+ T cells expressing Eomes exhibit enhanced mitochondrial functions, which resulted in their increased capacity to survive upon prolonged in vitro stimulation. Together, our data reveal a new mechanism by which Eomes promotes severity and chronicity of inflammation via the enhancement of CD4+ T cell mitochondrial functions and resistance to stress-induced cell death.
2023-12-23 | GSE247862 | GEO
Project description:The T-box transcription factors T-bet and Eomesodermin regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is widely expressed in the immune system but was initially identified as the lineage-specifying transcription factor of Th1 CD4+ T cells, where it governs expression of the signature cytokine IFN-g and represses alternative cell fates like Th2 and Th17. T-bet’s paralog Eomes is less abundantly expressed and Eomes+ CD4+ T cells can mostly be found in the context of persistent antigen exposure, like bone marrow transplantation, chronic infection or inflammation as well as malignant disorders. However, it has remained unresolved whether Eomes executes similar transcriptional activities as T-bet in CD4+ T cells. Here we show in a novel genetic model that the expression of Eomes in CD4+ T cells drives a distinct transcriptional program that shows only partial overlap with T-bet. We found that Eomes was sufficient to induce the expression of the immunoregulatory cytokine IL-10 and, together with T-bet, promoted a cytotoxic effector profile, including Prf1, Gzmb, Gzmk, Nkg7 and Ccl5, while repressing alternative cell fates. Our results demonstrate that Eomes+ CD4+ T cells, which are often found in the context of chronic antigen stimulation, are likely to be a unique CD4+ T cell subset with the potential to limit inflammation and immunopathology as well as to eliminate antigen-presenting and malignant cells.
2023-01-19 | GSE213980 | GEO
Project description:The presence of the PTPN22 risk variant (1858T) is associated to several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk variant on T cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve CD4+ T cells carrying two PTPN22 risk alleles overexpress a limited number of genes including CFLAR and 4-1BB important for cytotoxic T cell differentiation. Moreover, an increased number of cytotoxic EOMES+ CD4+ T cells were observed in PTPN22 risk allele carriers, which negatively correlated with a decreased number of naïve T cells in older individuals. No difference in the frequency of other CD4+ T cell subsets (Th1, Th17, Tfh, Treg) was observed in PTPN22 risk allele carriers and Treg suppressive capacity was not altered. Finally, in synovial fluids of RA patients, an accumulation of EOMES+ CD4+ T cells was observed with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, our data provide a novel mechanism of action of PTPN22 risk variant on CD4+ T-cell differentiation and identify EOMES+ CD4+ T cell as a relevant T cell subset in RA.
2018-02-27 | GSE94859 | GEO
Project description:Eomesodermin (Eomes) is a transcription factor with a crucial role regulating cytotoxic function, development and survival of immune cells. Although it is known that γδ T cells can express Eomes, its function on those cells is still largely unknown. Using Eomes-IRES-GFP mice we were able to sort for Eomes+ and Eomes‒ γδ T cells populations and get their gene expression profiles, bringing light to the role of Eomes on γδ T cells.
2017-04-10 | GSE85585 | GEO
Project description:High amount of Eomes might drive T cell exhaustion. In order to understand how Eomes contributes to exhaustion of CD8+ T cell in the TME as a transcription factor, we conducted anti-Eomes ChIPseq analysis of control OT-I cells and Eomes-overexpressing OT-I cells.
2018-11-26 | GSE122888 | GEO
Project description:IL-10-producing CD4+ type-1 regulatory T cells (Tr1) promote immune tolerance during chronic infection, autoimmunity, and transplantation. However, specific Eomes-dependent stages of Tr1 differentiation and function remain unclear. Using preclinical models of bone marrow transplantation (BMT) and chimeric antigen receptor (CAR) T cell immunotherapy, we demonstrate a Tr1 differentiation trajectory in vivo from Eomes+IL-10– to Eomes+IL-10+ subsets with the acquisition of cytokine, cytolytic and exhaustion features. The Eomes+CD4+ fraction represents the dominant cytotoxic subset after BMT, mediating graft-versus-leukemia effects while limiting inflammation. In CD19-targeted CAR T cell immunotherapy, Eomes drives the same CD4+ Tr1 phenotype that controls cytolysis, whilst mitigating immune toxicity and promoting persistence. In patients receiving commercial CD19-targeted CAR T cells with long term disease control, Eomes+ Tr1 cells represent a stable population comprising 40-80% of the CD4+ CAR T cell population. Hence, Eomes controls both regulatory and cytotoxic programs in CD4+ T cells, essential for curative immunotherapy outcomes.
2025-10-01 | GSE305624 | GEO
Project description:IL-10-producing CD4+ type-1 regulatory T cells (Tr1) promote immune tolerance during chronic infection, autoimmunity, and transplantation. However, specific Eomes-dependent stages of Tr1 differentiation and function remain unclear. Using preclinical models of bone marrow transplantation (BMT) and chimeric antigen receptor (CAR) T cell immunotherapy, we demonstrate a Tr1 differentiation trajectory in vivo from Eomes+IL-10– to Eomes+IL-10+ subsets with the acquisition of cytokine, cytolytic and exhaustion features. The Eomes+CD4+ fraction represents the dominant cytotoxic subset after BMT, mediating graft-versus-leukemia effects while limiting inflammation. In CD19-targeted CAR T cell immunotherapy, Eomes drives the same CD4+ Tr1 phenotype that controls cytolysis, whilst mitigating immune toxicity and promoting persistence. In patients receiving commercial CD19-targeted CAR T cells with long term disease control, Eomes+ Tr1 cells represent a stable population comprising 40-80% of the CD4+ CAR T cell population. Hence, Eomes controls both regulatory and cytotoxic programs in CD4+ T cells, essential for curative immunotherapy outcomes.
2025-10-01 | GSE305683 | GEO