Gene expression of sorted Eomes+ and Eomes‒ γδ T cells from spleen of Eomes-IRES-GFP mice.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE85585 | GEO | 2017/04/10
SECONDARY ACCESSION(S): PRJNA338885
REPOSITORIES: GEO
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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.
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Project description: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.
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Project description:The Tbx factors Eomesodermin (Eomes) and Brachyury instruct endoderm and mesoderm specification. Both Tbx factors have common large overlap in chromatin binding sites, however their embryonic phenotypes of mutants largely differ. In this study, we delineate the distinct binding patterns and gene target sets of Eomes and Brachyury providing a molecular model of distinct fate specification programs.
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Project description:Gene expression of sorted Eomes+ and Eomes‒ γδ T cells from spleen of Eomes-IRES-GFP mice.
| PRJNA338885 | ENA
Project description:Abstract: Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterize differential gene expression in γδ T cells – a subgroup of T cells which bridge innate and adaptive immunity and have specific anti-mycobacterial response mechanisms. γδ T cell subsets are classified on the basis of expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB infection may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10-12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 163 genes were significantly differentially expressed in the M. bovis-infected compared to control groups for the WC1.1+ γδ T cell compartment (Log 2 FC ≥ 1.5 and FDR P adj ≤ 0.1). The majority of these DEGs (146) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factor (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM and GZMH) and multiple killer cell immunoglobulin-like receptors (KIR) indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis and cytotoxicity of lymphocytes. In conclusion, WC1.1+ γδ T cells have been proposed as major regulatory cell subset in cattle, and we provide evidence for preferential differential activation of this specific subset in cattle naturally infected with M. bovis. Understanding the role of these critical immune cells during mycobacterial infection contributes to our understanding of host immunity to bTB and identifies multiple novel cytotoxic functions of WC1.1+ γδ T cells.
2023-07-01 | E-MTAB-13111 | biostudies-arrayexpress
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 | GSE124912 | GEO
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
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 | GSE124913 | 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 | GSE247862 | GEO