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TGF-b and Eomesodermin coordinate to maintain CD8+ regulatory T cells and limit spontaneous germinal center reaction

ABSTRACT: TGF-b and Eomesodermin coordinate to maintain CD8+ regulatory T cells and limit spontaneous germinal center reaction

PROVIDER: PRJNA515265 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8444137.fastq.gz	Fastqsanger.gz
	SRR8444138.fastq.gz	Fastqsanger.gz

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Similar Datasets

TGF-b and Eomesodermin coordinate to maintain CD8+ regulatory T cells and limit spontaneous germinal center reaction

Project description:We are interested in CD8+ regulatory T cells that limit germinal center reactions. We have found that in conditional knockout mice lacking both Tgfbr2 and Eomes expression in mature T cells, CD8+ regulatory T cells are severely defective. RNA-seq analysis was employed to characterize the genome-wide transcriptional changes in CD8+ regulatory T cells.

2020-09-17 | GSE125111 | GEO

Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

Project description:The Germinal center is a dynamic microenvironment wherein B cells expressing high affinity antibody variants produced by hypermutation are selected for clonal expansion by limiting numbers of T follicular helper cells. Although a great deal is known about the mechanisms that control B cell selection in the germinal center, far less is understood about the clonal behavior of the T follicular helper cells that regulate this process. Here we report on the dynamic behavior of clones of T follicular helper cells during the germinal center reaction. We find that like germinal center B cells, T follicular helper cells undergo antigen dependent selection during the germinal center reaction resulting in differential proliferative expansion and contraction. Increasing the amount of antigen presented in the germinal center leads to increased T follicular cell division. Competition between T follicular helper cell clones is mediated by T cell receptor affinity for peptide-MHC ligand. Higher affinity T cells expanding preferentially in the germinal center show increased expression of genes downstream of the T cell receptor, genes required for metabolic reprogramming, cell division and cytokine production. These dynamic changes lead to dramatic remodeling of the functional T follicular cell repertoire during the germinal center reaction.

2020-03-19 | GSE147182 | GEO

Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

Project description:Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

| PRJNA613275 | ENA

Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

Project description:Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

| PRJNA591861 | ENA

Pluripotency Factors Regulate Definitive Endoderm Specification through Eomesodermin

Project description:Understanding the molecular mechanisms controlling early cell fate decisions in mammals is a major objective towards the development of robust methods for the differentiation of human pluripotent stem cells into clinically relevant cell types. Here, we used human embryonic stem cells (hESCs) to study specification of definitive endoderm in vitro. Using a combination of whole genome expression and ChIP-seq analyses, we established a hierarchy of transcription factors regulating endoderm specification. Importantly, pluripotency factors, namely NANOG, OCT4 and SOX2 have an essential function in this network by actively directing differentiation. Indeed, these transcription factors control the expression of EOMES, which marks the onset of endoderm specification. In turn, EOMES interacts with SMAD2/3 to initiate the transcriptional network governing endoderm formation. Together, these results provide for the first time a comprehensive molecular model connecting the transition from pluripotency to endoderm specification during mammalian development. ChIP-Seq of Eomesodermin binding in human embyonic stem cells, differentiated towards an endodermal fate for 48h in chemically-defined culture media. Includes an input DNA control. Supplementary file GSE26097_README.txt contains descriptions of the raw data files and processed data files.

2011-01-25 | E-GEOD-26097 | biostudies-arrayexpress

Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

Project description:Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

| PRJNA805304 | ENA

Cytolytic CD8<sup>+</sup> T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes.

Project description:Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

| S-EPMC10231436 | biostudies-literature

Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

Project description:Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer to the B cell of a very restricted set of T cell EV-microRNAs (mmu-miR20a-5p, mmu-miR-25-3p and mmu-miR-155-3p). Transferred EV-microRNAs target key genes that control B cell function, including the pro-apoptotic BIM and the cell-cycle regulator PTEN. EV-microRNAs transferred in T-B cognate interactions also promote survival, proliferation and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that small EV transfer is required for the germinal center reaction and antibody production in vivo, revealing a novel mechanism that controls B cell responses through the transfer of EV-microRNAs of T cell origin. These findings provide mechanistic insight on the Griscelli syndrome, associated with a mutation in the Rab27a gene and may shed light on this pathogenesis and other immune-related and inflammatory disorders. This SuperSeries is composed of the SubSeries listed below.

2020-01-20 | GSE141045 | GEO

Germline competency of human embryonic stem cells depends on eomesodermin

Project description:In humans, germline competency and the specification of primordial germ cells (PGCs) are thought to occur in a restricted developmental window during early embryogenesis. Despite the importance of specifying the appropriate number of PGCs for human reproduction, the molecular mechanisms governing PGC formation remain largely unexplored. Here, we compared PGC-like cell (PGCLC) differentiation from 18 independently derived human embryonic stem cell (hESC) lines, and discovered that the expression of primitive streak genes were positively associated with hESC germline competency. Furthermore, we show that chemical inhibition of TGFβ and WNT signaling, which are required for primitive streak formation and CRISPR/Cas9 deletion of Eomesodermin (EOMES), significantly impacts PGCLC differentiation from hESCs. Taken together, our results suggest that human PGC formation involves signaling and transcriptional programs associated with somatic germ layer induction and expression of EOMES.

2018-11-10 | GSE93126 | GEO

Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

Project description:Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

2023-04-20 | GSE196549 | GEO

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