Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic analysis of TCF-7 cKO CD4 T cells

ABSTRACT: The transcription factor T Cell Factor-1 encoded by (TCF-7) is critical for T cell development. However, the role of TCF-7 on peripheral CD4 T cells mediated allo-immunity was not known. In this report using a clinically relevant model we presented novel finding of how TCF-7 regulates CD4 T cells functions, including CD4 T cells activation, proliferation, differentiation and impacts effector and central memory formation. We uncovered how TCF-7 regulates chemokine receptor which are essential for CD4 T cells migration to the site of inflammation. Our data uncovered how TCF-7 plays critical role in CD4 T cells survival, apoptosis. Using in vivo allo-immunity models and in-vitro studies we demonstrated how TCF-7 plays central role in CD4 T cells mediated damaged to organs like liver, skin and small intestine. We provided both molecular and biochemical and transcriptomic evidence how TCF-7 functionally regulates CD4 T cells mediated apoptosis and cell death, T cell mediated processes, pro-inflammatory and anti-inflammatory cytokines productions in both basal level and after allo-activation. These findings novel findings represent a stem forward to designing target specific approach for CD4 T cells mediated diseases while understand molecular mechanism the role of CD4 T cells in allo-immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE204747 | GEO | 2022/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of human monocyte-derived dendritic cells to study uptake of apoptotic cells by dendritic cells and induction of T-cell immunity

Project description:The identification of molecules for apoptotic cells (AC) uptake by dendritic cells (DCs) and induction of T cell immunity is a major challenge in immunology.<br>DCs generated from monocytes in the presence of IFN-alpha (IFN-alpha-DCs) are competent in taking up ACs and inducing a strong T cell immunity. Capture of allogenetic apoptotic lymphocytes (APO-allo-PBLs) was associated with subcellular rearrangements of MHC class I/II molecules, subsequent cross-priming of auologous CD8+ T cells and CD4+ T cell activation. All these events were inhibited by the Scavenger Receptor (SR) LOX-1 protein, whose expression was up-regulated in IFN-alpha DCs. The results unravel a novel natural IFN-alpha-mediated pathway by which a defined SR molecule regulates AC uptake by DCs and subsequent induction of T cell immunity.

2010-01-08 | E-MEXP-2000 | biostudies-arrayexpress

Transcriptomic analysis of TCF-7 cKO CD8 T cells

Project description:T Cell Factor-1, encoded by TCF-7, is a transcription factor that plays an essential role during T cell development and differentiation. In this manuscript we utilized a pre-clinical model provided evidence that TCF-7 is dispensable for the anti-tumor response, and that TCF-7 suppresses key transcriptional factors Eomes and T-bet and molecules responsible for peripheral CD8 T cell cytolytic function. We discovered that TCF-7 regulates NKG2D expression on naïve and activated mouse CD8 T cells, and that peripheral CD8 T cells from TCF-7 cKO utilize NKG2D to clear tumor cells. We also provide evidence that TCF-7 regulates key signaling molecules, including LCK, LAT, ITK, PLC-y1, P65, ERKI/II, and JAK/STATs required for peripheral CD8 T cell persistent function. Our data transcriptomic and protein data uncovered the mechanism of how TCF-7 impacting peripheral CD8 T cell inflammatory cytokine production, CD8 T cell activation, and apoptosis. Our pre-clinical model showed that CD8 T cells from TCF-7 cKO mice did not cause GVHD, but effectively cleared primary tumor cells.

2022-06-30 | GSE203167 | GEO

Whole-transcriptome quantitative analysis of WT versus Ikzf3-/- CD4+ T cells cultured in Th1-polarizing or Tfh-polarizing conditions

Project description:Effective immunity to viruses such as influenza and SARS-CoV-2 requires the generation of CD4+ T cell subsets that coordinate complementary aspects of the immune response. These include T follicular helper (TFH) and T helper 1 (TH1) cells, which promote humoral and cell-mediated helper responses, respectively. A third population, CD4+ cytotoxic T lymphocytes (CD4-CTLs) facilitates clearance of infection via mechanisms normally associated with CD8+ T cells, including perforin-mediated destruction of infected cells. Here, we identify the transcription factor Aiolos as a reciprocal regulator of TFH and CD4-CTL responses. We demonstrate that Aiolos deficiency compromises TFH differentiation and antibody production during influenza infection. Conversely, we find that CD4+ T cells acquire a cytotoxic-like program in the absence of Aiolos, including increased expression of the CTL-associated transcription factors Eomes and Blimp-1. We further show that while Aiolos positively regulates the TFH transcriptional regulators Zfp831, Tcf-1 and Bcl-6, it also directly represses expression of IL-2Ra and IL-2/STAT5-driven expression of the cytotoxic gene program. Thus, our findings identify Aiolos as a pivotal regulator of TFH and CD4-CTL differentiation and highlight its potential as a therapeutic target for the manipulation of CD4+ T cell humoral and cytotoxic responses.

2023-02-01 | GSE203065 | GEO

ATAC-seq analysis of WT versus Ikzf3-/- CD4+ T cells cultured in Th1-polarizing or Tfh-polarizing conditions

2023-02-01 | GSE203064 | GEO

Host NLRP6 exacerbates graft-versus-host disease independent of microbial diversity

Project description:Host NLRP6 regulates innate immune responses and gastrointestinal (GI) homeostasis. It plays a protective role in pathogenic processes such as intestinal colitis and tumorigenesis in a microbiome dependent manner. Host innate immunity and changes in microbial diversity also play a role in the severity of allo-immune-mediated gastrointestinal pathogenic process, namely graft-versus-host disease (GVHD), the principal toxicity after allogeneic bone marrow transplantation (allo-BMT). Herein, we examined the role of NLRP6 in multiple murine models of allo-BMT. In contrast to its role in intestinal colitis, host NLRP6 aggravated GI GVHD. NLRP6-deficient animals showed improved intestinal barrier function, increased levels of tissue repair associated proteins and preserved Goblet and Paneth cell numbers in the GI tract after allo-BMT. The impact of host NLRP6 deficiency in mitigating GVHD was observed regardless of co-housing, antibiotic treatment, or colonizing littermate germ free wild type (WT) and NLRP6 deficient hosts with fecal microbial transplantation from SPF WT and Nlrp6-/- animals. Chimera studies were performed to assess the role of NLRP6 expression on host hematopoietic and non-hematopoietic cells. The allogeneic [B6Ly5.2→Nlrp6-/-] animals demonstrated significantly improved survival compared to the allogeneic [B6Ly5.2→B6] animals, demonstrating that the absence of NLRP6 in host non-hematopoietic cells is crucial for the protection against GVHD, but did not alter the therapeutic graft-versus-tumor effects after BMT. Our results unveil a novel role for NLRP6 and demonstrate a pathogenic role in GVHD that is independent of variations in its intestinal microbiome in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis.

2018-11-05 | ST001089 | MetabolomicsWorkbench

A genetic screen in macrophages identifies new regulators of IFNg-inducible MHCII that contribute to T cell activation

Project description:Cytokine-mediated activation of host immunity is central to the control of pathogens. Interferon-gamma (IFNg) is a key cytokine in protective immunity that induces major histocompatibility complex class II molecules (MHCII) to amplify CD4+ T cell activation and effector function. Despite its central role, the dynamic regulation of IFNg-induced MHCII is not well understood. Using a genome-wide CRISPR-Cas9 screen in murine macrophages we globally identified genes that control MHCII surface expression. Mechanistic studies uncovered two parallel pathways of IFNg-mediated MHCII control that require the multifunctional glycogen synthase kinase 3 beta (GSK3b) or the mediator complex subunit MED16. Both pathways control distinct aspects of the IFNg response and are necessary for IFNg-mediated induction of the MHCII transactivator CIITA, MHCII expression, and CD4+ T cell activation. Our results define previously unappreciated regulation of MHCII expression that is required to control CD4+ T cell responses.

2021-11-01 | GSE162464 | GEO

Liver X receptor controls follicular helper T cell differentiation via repression of TCF-1

Project description:Liver X receptor (LXR) is a critical regulator of cholesterol homeostasis, and inhibits TCR-induced proliferation by altering intracellular sterol metabolism. However, the mechanisms by which LXR regulates helper T cell subset differentiation in vivo remains unclear. Here we demonstrate here that LXR is a crucial regulator of follicular helper T (Tfh) cells in vivo. Both mixed bone marrow chimera and antigen-specific T cell adoptive co-transfer studies show a specific increase in Tfh cells among LXRβ-deficient CD4+ T cell population in response to immunization and LCMV infection. Mechanistically LXRβ-deficient Tfh cells express increased levels of TCF-1 but comparable levels of Bcl6, CXCR5, and PD-1 in comparison with LXRβ-sufficient Tfh cells. Loss of LXRβ confers inactivation of GSK3β induced by either AKT/ERK activation or Wnt/β-catenin pathway, leading to elevated TCF-1 expression in CD4+ T cells. Conversely, ligation of LXR represses TCF-1 expression and Tfh cell differentiation in both murine and human CD4+ T cells. Treatment with an LXR agonist significantly diminishes Tfh cells and the levels of antigen-specific IgG upon immunization. These findings unveil a novel cell-intrinsic regulatory function of LXR in Tfh cell differentiation via controlling GSK3β-TCF1 pathway, which might be a promising target for pharmacological intervention in Tfh-mediated diseases.

2023-02-06 | GSE224303 | GEO

scRNA-seq of allo-reactive CD4+ T cells

Project description:scRNA-seq of allo-reactive CD4+ T cells

| PRJEB38712 | ENA

scRNA-seq of allo-reactive CD4+ T cells

Project description:Acute graft versus host disease is a serious condition caused by allo-reactive donor CD4+ T cells from allogenic hematopoietic stem cell transplantation. To understand the developmental relationships between T-helper states in mesenteric lymph nodes (mLN), TCR transgenic CD4+ T cells specific for a single allo-peptide (TEa cells) from mice were recovered at Days 0, 1, 2, 3, and 4 from mLN, and Day 5 from the gut and underwent processing to generate scRNA-seq dataset. TEa cells were also recovered at Day 5 from mLN and were either treated with and without IEL-isolation pre-digestion buffer as controls.

2020-06-06 | E-MTAB-9125 | biostudies-arrayexpress

Single-cell RNA sequencing revealed the role of the Th17 pathway in the development of anti HLA antibodies in a highly sensitized mouse model

Project description:The aim of this study is to investigate the specific pathway involved in HLA sensitization using single-cell RNA sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse. For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg (HLA-A2.1)1Enge/J mouse (allogeneic mouse (ALLO)). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA sequencing analysis on splenocytes isolated from ALLO and SYN mice and compared the gene expression between them. We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN control mice, respectively. Five major cell types (B-cells, T-cells, NK cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B-cells was higher in allogeneic mouse than it was in syngeneic control mouse. KEGG enrichment analyses indicated that the highly expressed genes in the B-cells from ALLO mouse were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T-cells of ALLO mouse were involved in the IL-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO mouse. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO mouse compared to those in the SYN mouse. Our results indicate that not only the B cell lineage, but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

2024-08-15 | GSE240862 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data