Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiling of WT and STAT3-/- Tc17 CD8+ T cells

ABSTRACT: CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (‘Tc17’) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the ‘cytotoxic’ transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.

ORGANISM(S): Mus musculus

PROVIDER: GSE104144 | GEO | 2017/11/27

SECONDARY ACCESSION(S): PRJNA411814

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression profiling of Tc1 and Tc17 CD8+ T cells

Project description:CD8+ T cells are pre-programmed for cytotoxic differentiation. However, a subset of effector CD8+ T cells (‘Tc17’) produce IL-17 and fail to express cytotoxic genes. Here, we show that the transcription factors directing IL-17 production inhibit cytotoxicity despite persistent Runx3 expression. Cytotoxic gene repression did not require the transcription factor Thpok. We further show that STAT3 restrained cytotoxic gene expression in CD8+ T cells and that RORgt represses cytotoxic genes by inhibiting the functions but not the expression of the ‘cytotoxic’ transcription factors T-bet and Eomesodermin. Thus, the transcriptional circuitry directing IL-17 expression inhibits cytotoxic functions.

2017-11-27 | GSE104143 | GEO

Tc17 cells are a pro-inflammatory, plastic lineage of pathogenic CD8+ T-cells that induce GVHD without anti-leukemic effects

Project description:IL-17-producing cells are important mediators of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Here we demonstrate that a distinct CD8+ Tc17 population develops rapidly after SCT but fails to maintain lineage fidelity such that they are unrecognizable in the absence of a fate reporter. Tc17 differentiation is dependent on alloantigen presentation by host-DC together with IL-6. Tc17 cells express high levels of multiple prototypic lineage-defining transcription factors (e.g. RORgt, T-bet) and cytokines (e.g. IL-17A, IL-22, IFNg, GM-CSF, IL-13). Targeted depletion of Tc17 early after transplant protects from lethal acute GVHD, however Tc17 cells are non-cytolytic and fail to mediate graft–versus–leukemia (GVL) effects. Thus, the Tc17 differentiation program during GVHD culminates in a highly plastic, hyper-inflammatory, poorly-cytolytic effector population which we term inflammatory Tc17 (iTc17). Since iTc17 mediate GVHD without contributing to GVL, therapeutic inhibition of iTc17 development in a clinical setting represents an attractive approach for separating GVHD and GVL. Single colour, Illumina MouseRef-8 v2.0 Beadarrays.

2015-09-13 | E-GEOD-70931 | biostudies-arrayexpress

RNAseq of (Dimethylfumarate)DMF-induced changes in murine Tc17 CD8+ cells

Project description:IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy.

2018-07-11 | GSE116866 | GEO

Tc17 cells are a pro-inflammatory, plastic lineage of pathogenic CD8+ T-cells that induce GVHD without anti-leukemic effects

2015-09-13 | GSE70931 | GEO

RNAseq of (Dimethylfumarate)DMF-induced changes in human CD8+ memory cells

2018-07-11 | GSE116865 | GEO

Developmental self-reactivity determines the pathogenic Tc17 differentiation potential of naive CD8+ T cells by adjusting endogenous SMAD3 expression

Project description:The differentiation of naive CD8+ T cells into effector cells is important for establishing immunity. However, the effect of heterogeneous naive CD8+ T cell populations is not fully understood. Here, we demonstrate that steady-state naive CD8+ T cells are composed of functionally heterogeneous subpopulations that differ in their ability to differentiate into type 17 cytotoxic effector cells (Tc17) in inflammatory disease models. The differential ability of Tc17 differentiation was not related to T-cell receptor (TCR) diversity and antigen specificity but was inversely correlated with self-reactivity acquired during development. Mechanistically, this phenomenon was linked to differential levels of intrinsic TCR sensitivity and basal SMAD3 expression, generating a wide spectrum of Tc17 differentiation potential within naive CD8+ T cell populations. These findings suggest that developmental self-reactivity can determine the fate of naive CD8+ T cells to generate functionally distinct effector populations and achieve immense diversity and complexity in antigen-specific T-cell immune responses.

2023-08-15 | GSE240440 | GEO

TCF-1 regulation of CD8+ T cell chromatin accessibility

Project description:CD8+ T cell differentiation traditionally results in the emergence of two subsets, Tc1 cells that produce interferon (IFN)-gamma and memory cells that mediate immune protection against pathogen infections. More recently, it has emerged that other specialized CD8+ T cell populations develop in immune responses and are critical to orchestrate complete immune protection. These subsets include tissue-resident memory (Trm) T cells, follicular cytotoxic T cells and two CD8+ T cell subsets that produce interleukin (IL)-17, namely, mucosal-associated invariant T (MAIT) cells and Tc17 cells. Here we investigated the role of TCF-1 in CD8+ T cell differentiation by using Assay for Transposase-Accessible Chromatin sequencing (ATAC-Seq) to determine the chromatin accessibility landscape of CD8+ T cells and how this is controlled by TCF-1. Loss of TCF-1 was associated with global changes in the chromatin architecture in CD8+ T cells leading to increased accessibility of Rorc and Tc17 effector genes IL-17a and IL-17f in Tc17 cells. In contrast, we observed reduced accessibility of Tbx21, Eomes and Irf4 loci in Tc17 cells, genes normally required for the induction of Tc1 and memory CD8+ T cells

2019-05-14 | GSE119839 | GEO

Single cell RNA-seq of psoriatic skin identifies pathogenic Tc17 subsets and reveals distinctions between CD8+ T cells in autoimmunity and cancer

Project description:Psoriasis is an inflammatory, IL-17-driven skin disease in which autoantigen-induced CD8+ T cells have been identified as pathogenic drivers. In this study, we used single-cell RNA-seq to identify 11 transcriptionally diverse CD8+ T cell subsets in psoriatic and healthy skin. Among several inflammatory subsets enriched in psoriatic skin, we observed two Tc17 subsets that were metabolically divergent, developmentally related, and expressed CXCL13, which we found to be a biomarker of psoriasis severity. Despite high co-inhibitory receptor expression in the Tc17 clusters, a comparison of these cells with melanoma-infiltrating CD8+ T cells revealed upregulated cytokine, cytolytic, and metabolic transcriptional activity in the psoriatic cells that differed from an exhaustion program. Our findings provide a high-resolution view of cutaneous CD8+ T cells in psoriasis and healthy skin and shed light on their functional distinctions within the chronic pathologies of autoimmunity and cancer.

2021-01-05 | GSE146264 | GEO

mRNAseq of murine PancOVA tumor cells after coculture with Tc17 conditioned -iCafs or Tc17 cells

Project description:we examined the influence of Tc17 conditioned -iCafs or Tc17 cells on the in vitro differentiation of murine PancOVA tumor cells

2023-02-10 | GSE218816 | GEO

Transcriptional Reprogramming of Mature CD4 T helper Cells generates distinct MHC class II restricted Cytotoxic T Lymphocytes

Project description:We show here that the T helper-fate is not fixed and that mature antigen-stimulated CD4 T cells can switch off Thpok expression and reactivate CD8- lineage genes. This unexpected plasticity results in the post-thymic termination of the T helper- program and the functional differentiation of distinct MHC class II restricted CD4 cytotoxic T lymphocytes Small intestine CD4 intraepithelial T lymphocytes from ThPOK-GFP reposter mice were isolated and sorted (FACS Aria) based on ThPOK and CD8aa expression. Cell were isolated either from non-experimental ThPOK-GFP reporter mice (WT) or after transfering CD4 naive T cells from ThPOK-GFP reporter mice to RAG-/-recipient animals (TR) as an experimental colitis model. Experimet was done in duplicate.

2012-12-10 | E-GEOD-42277 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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