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Expression data from Eomes+ and Eomes- CD8 T cells following aOX40/aCTLA-4 treatment

ABSTRACT: Development, maturation, and function of CD8 T cells is regulated by transcription factor expression. Expression of the transcription factor Eomesodermin was found to be significantly increased in CD8 T cells following aOX40/aCTLA-4 immunotherapy in mice. We used microarray analysis to detail gene expression in Eomes+ and Eomes- CD8 T cells following aOX40/aCTLA-4 treatment to determin functional differences between these two populations.

ORGANISM(S): Mus musculus

PROVIDER: GSE166532 | GEO | 2021/02/11

REPOSITORIES: GEO

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EOMES interacts with RUNX3 and BRG1 to promote innate memory cell formation through epigenetic reprogramming

Project description:Memory CD8+ T cells have the ability to provide lifelong immunity against pathogens. Although memory features generally arise after challenge with a foreign antigen, naïve CD8 single positive (SP) thymocytes may acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these innate memory CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming is secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, EOMES is found within chromatin-associated complexes containing BRG1 and promotes the recruitment of this chromatin remodelling factor. Also, the in vivo acquisition of EOMES-dependent program is BRG1-dependent. In conclusion, our results support a strong epigenetic basis for the EOMES-driven establishment of CD8+ T cell innate memory program.

2019-06-06 | PXD014142 | Pride

Gene expression of sorted Eomes+ and Eomes‒ γδ T cells from spleen of Eomes-IRES-GFP mice.

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.

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EOMES-dependent epigenetic reprogramming during CD8 T cell development leads to acquisition of memory traits (ATAC-Seq)

Project description:Memory CD8 T cells have a unique ability to provide lifelong immunity against pathogens. Although memory features generally arise after a challenge with foreign antigen, naïve CD8 single positive (SP) thymocytes may already acquire phenotypic and functional characteristics of memory cells in response to cytokines such as interleukin-4. This process is associated with the induction of the T-box transcription factor Eomesodermin (EOMES). However, the underlying molecular mechanisms remain ill-defined. Using epigenomic profiling, we show that these “innate memory” CD8SP cells acquire only a portion of the active enhancer repertoire of conventional memory cells. This reprograming was secondary to EOMES recruitment, mostly to RUNX3-bound enhancers. Furthermore, we identified direct interaction between EOMES and BRG1 and showed that in vivo acquisition of EOMES-dependent program by CD8SP thymocytes was dependent on this chromatin remodeling factor. In conclusion, our results support a strong epigenetic basis for EOMES-driven establishment of CD8 T cell unconventional memory program.

2019-06-06 | GSE124911 | GEO

EOMES-dependent epigenetic reprogramming during CD8 T cell development leads to acquisition of memory traits (RNA-Seq)

2019-06-06 | GSE124913 | GEO

EOMES-dependent epigenetic reprogramming during CD8 T cell development leads to acquisition of memory traits (ChIP-Seq)

2019-06-06 | GSE124912 | GEO

anti-Eomes ChIPseq of control OT-I cells and Eomes-overexpressing OT-I cells

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.

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A comparison of the transcriptional profiles of invariant NKT cells derived from Wild type and Eomes conditional knockout mice

Project description:Functional subsets of iNKT cells, NKT1, NKT2 and NKT17, have been reported to arise during the thymus to peripheral differentiation stages. The key transcription factors for NKT1, NKT2 and NKT17 development in the thymus have been identified as T-bet, Gata3 and Rorγt, respectively. In contrast, these iNKT cell subsets can also undergo further differentiation in the periphery. Eomesodermin (Eomes) is a T-box transcription factor with high homology to T-bet and is expressed by activated CD8+ T cells as well as in resting and activated NK cells. However, its role in invariant (i)NKT cells remains unknown. Here, we show the impact of Eomes on iNKT cells in the thymus and peripheral tissue using conditional knockout (Eomes-cKO) mice. Eomes regulates the differentiation of NKT1 cells in the thymus. In the peripheral tissue, Klrg1+ iNKT1 cells are generated in lung after vaccination with -GalCer-pulsed DCs (DC/Gal) as memory like iNKT cells. In the current study, we found that Eomes also regulates their differentiation into memory-like KLRG1+iNKT cells in the periphery.

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Expression data from Eomes+ and Eomes- CD8 T cells following aOX40/aCTLA-4 treatment

Project description:Expression data from Eomes+ and Eomes- CD8 T cells following aOX40/aCTLA-4 treatment

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Eomes identifies thymic precursors of self-specific memory-phenotype CD8+ T cells

Project description:Unprimed mice harbor a substantial population of "memory-phenotype" CD8+ T cells (CD8-MP cells) that exhibit hallmarks of activation and innate-like functional properties. Due to the lack of faithful markers to distinguish CD8-MP cells from bona fide CD8+ memory T cells, the developmental origins and antigen specificities of CD8-MP cells remain incompletely defined. Using deep T cell receptor (TCR) sequencing, we found that the TCRs expressed by CD8-MP cells are highly recurrent and distinct from the TCRs expressed by naive-phenotype CD8+ T cells. CD8-MP clones exhibited reactivity to widely expressed self-ligands. T cell precursors expressing CD8-MP TCRs upregulated the transcription factor Eomes during maturation in the thymus, prior to induction of the full memory phenotype, suggestive of a unique program triggered by recognition of self-ligands. Moreover, CD8-MP cells infiltrate oncogene-driven prostate tumors and express high densities of PD-1, suggesting a potential role in anti-tumor immunity and response to immunotherapy.

2020-03-23 | GSE145365 | GEO

Eomes regulates mitochondrial function and promotes survival of pathogenic CD4+ T cells during chronic inflammation [RNA-seq]

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

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