Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional profiling of CD4+ T cells with high, intermediate and low PD-1 and ICOS co-expression from HCV infected chimpanzees

ABSTRACT: A sustained CD4+ T cell response is required for resolution of acute HCV infection but remains poorly characterized. Here, CD4+ T cells with high PD-1 and ICOS co-expression expanded in the blood of chimpanzees during acute HCV infection. The peak response was comprised primarily of HCV-specific populations and temporally associated with acute hepatitis, seroconversion, and initial control of HCV replication. Circulating PD-1hiICOShi CD4+ T cells differentially expressed genes associated with Tfh, Th1, and cytotoxic signatures. Co-production of Tfh (CXCL13, IL-21) and Th1 (IFN-) effector molecules was observed after HCV antigen stimulation. HCV-specific Tfh1 CD4+ T cells infiltrated liver, consistent with expression of chemokine receptors that mediate homing to inflamed tissues. Most were CXCR5-negative and therefore resembled Tph/Tfhx13 CD4+ T cells recently described in cancer and autoimmune conditions. Detailed transcriptional, phenotypic, and functional analysis of the protective CD4+ T cell response presented here is expected to aid HCV vaccine development.

ORGANISM(S): Pan troglodytes

PROVIDER: GSE247812 | GEO | 2024/11/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

GM-CSF-induced CD40high human blood dendritic cells promote Tfh1 polarization

Project description:Using single-cell RNA sequencing (10X technology) on CD4+T cells, we report that GM-CSF-activated human blood CD1c+ dendritic cells (DC) (cDC2) drive the differentiation of naïve CD4+ T cells into Tfh1. These Tfh1 cells displayed typical Tfh molecular features, including high levels of PD-1, CXCR5, and ICOS. They co-expressed Bcl6 and T-bet, and secreted large amounts of IL-21 and IFN-γ.

2022-10-01 | GSE167364 | GEO

Non-coding autoimmune risk variant accelerates T peripheral helper cell development via ICOS

Project description:Fine-mapping and functional studies implicate rs117701653, a common non-coding variant in the CD28/CTLA4/ICOS locus, as a contributor to risk for rheumatoid arthritis and type 1 diabetes. Using DNA pulldown, mass spectrometry, genome editing and eQTL analysis, we establish that the disease-associated allele reduces affinity for the inhibitory chromosomal regulator SMCHD1 to drive expression of inducible T-cell costimulator (ICOS), enhancing memory CD4+ T cell ICOS expression in individuals bearing the risk allele. Higher ICOS expression is paralleled by an increase in circulating T peripheral helper (Tph) cells, and in rheumatoid arthritis patients, of blood and joint fluid Tph cells and circulating plasmablasts, suggesting a causal link. Indeed, ICOS ligation accelerates T cell differentiation into CXCR5-PD-1high Tph cells producing IL-21 and CXCL13, as does carriage of the rs117701653 risk allele. Thus, mechanistic dissection of a causal non-coding variant in human autoimmunity discloses a new pathway through which ICOS regulates Tph abundance.

2023-07-01 | GSE235868 | GEO

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus

Project description:SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL13, yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.

2024-07-08 | GSE233050 | GEO

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cell in lupus [Time_coure_RNAseq]

Project description:Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE), a prototypical autoimmune disease with broad autoantibody production. Human Tfh and Tph cells are marked by high production of the B cell chemoattractant CXCL13, yet regulation of T cell CXCL13 production and the relationship between a CXCL13+ state and other differentiated T cell states remains largely undefined. Here, we identify a dramatic imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.

2024-09-22 | GSE277730 | GEO

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus [JUN OE]

2024-07-08 | GSE233048 | GEO

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus [JUN AHR modulation]

2024-07-08 | GSE233047 | GEO

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus [JUN IFN]

Project description:SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL13 yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.

2024-07-08 | GSE252917 | GEO

Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus [AHR]

Project description:SLE is prototypical autoimmune disease driven by pathologic T cell-B cell interactions. Expansion of B cell-helper T cells including T follicular helper (Tfh) and T peripheral helper (Tph) cells is a prominent feature of systemic lupus erythematosus (SLE). Human Tfh and Tph cells characteristically produce high levels of the B cell chemoattractant CXCL135,6, yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4 T cell phenotypes in SLE patients, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4 T cells. Transcriptomic, epigenetic, and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ Tph/Tfh cell differentiation and promote an IL-22+ phenotype. Type I interferon (IFN), a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ Tph/Tfh cells on a polarization axis opposite from Th22 cells and reveal AHR, JUN, and IFN as key regulators of these divergent T cell states.

2024-07-08 | GSE233045 | GEO

PD-1highCXCR5–CD4+ Peripheral Helper T (Tph) cells Promote CXCR3+ Plasmablasts in the early phase of COVID-19

Project description:T cell–B cell interaction is the key immune response to protect host from severe viral infection. We used COVID-19 as a model of acute viral infections and analyzed CD4+ T cell subsets associated with plasmablasts expansion and clinical outcome. Peripheral helper T cells (Tph, denoted as PD-1highCXCR5–CD4+ T cells) were significantly increased, as were plasmablasts. Tph cells exhibited “B-cell help” signatures and induced plasmablasts differentiation in vitro. Expanded plasmablasts showed increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. These results elucidate a critical role for Tph cells in regulating protective B cell response during acute viral infection.

2023-01-05 | GSE214624 | GEO

P2X7 signaling drives Th1 cell differentiation through metabolic reprogramming for aerobic glycolysis

Project description:This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes Th1 cell differentiation. P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-polarized CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, ATP synthase blockade in vitro and the consequent inhibition of oxidative phosphorylation, which forces cells to use aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 cell differentiation and suggest that ATP synthase inhibition is a fundamental mechanism by which P2X7 signaling induces the Th1 response.

2023-03-08 | PXD037754 | Pride

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