Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel CD4+ T cell population expanded in SLE blood provides B cell help through IL10 and succinate

ABSTRACT: A better understanding of the mechanisms involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR5- CXCR3+ PD1hi CD4+ T cell ‘helper’ population distinct from follicular helper T cells (Tfh) and expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNand high levels of IL10. Additionally, they accumulate high amounts of mitochondrial ROS (mtROS) as the result of reverse electron transport (RET) fueled by succinate. These cells provide potent help to B cells through the synergistic effect of IL10 and succinate. Cells with similar phenotype and function are generated in vitro upon priming naïve CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)-activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118951 | GEO | 2018/09/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A novel CD4+ T cell population expanded in Systemic Lupus Erythematosus (SLE) blood provides B cell help through IL10 and succinate

Project description:A better understanding of the molecular and cellular factors involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR3+ PD1hi CD4+ T cell ‘helper’ population expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNg and IL10 and display high levels of mitochondrial ROS (mtROS) as the result of reverse electron transfer (RET) fueled by succinate. Furthermore, T cell-derived succinate synergizes with IL10 to provide B cell help. Cells with similar phenotype and function are generated in vitro upon priming naive CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)- activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE.

2018-09-26 | GSE109843 | GEO

Interleukin 10 and succinate synergize to provide B cell help in human lupus

Project description:Autoantibodies against nucleic acids are a hallmark of Systemic Lupus Erythematosus. We recently uncovered that human oxidized DNA of mitochondrial origin released by activated lupus neutrophils represents a distinct class of interferogenic TLR9 ligand for plasmacytoid dendritic cells. We now show that oxidized mitochondrial DNA-activated plasmacytoid dendritic cells skew naïve CD4+ T cells towards IL2low, IFNγhigh, IL10high secreting B helper cells different from follicular helper and Type 1 regulatory CD4+ T cells. Furthermore, PD1-induced succinate and mitochondrial ROS accumulation revoke anergy, while IL10 and succinate synergize to deliver B cell help. We provide evidence that IL10-producing CD4+ T cells infiltrate the SLE kidney insterstitium, where they might play a role in extrafollicular B cell responses. Thus, we describe a novel B cell helper pathway that links innate and adaptive immunity alterations in human lupus.

2018-09-26 | GSE93679 | GEO

A novel CD4 T cell population expanded in SLE blood provides B cell help through IL10 and succinate [ATAC-seq]

Project description:ATAC-seq analysis of CD4 T cell populations obtained in blood of systemic lupus erythematosus (SLE) patients. The overall goal of this study was to determine chromatin accessibility profiles in Tfh cells and CXCR3+ PD1hi CD4+ T cells obtained from blood of SLE donors.

2018-02-02 | GSE110017 | GEO

Gene expression profiles between mtROShigh and mtROSlow cells dissociated from E14.5 neocortical cells were compared by microarray

Project description:sample collection protocol:We used FACS to separate the E14.5 neocortical cells into high mitochondrial reactive oxygen species (mtROS) and low mitochondrial ROS cell populations and compared their expression profiles. Transition of progenitors through progressive stages of differentiation probably involves dynamic changes in mtROS levels, depending on the needs of the cell. We found that the progenitors had higher levels of mtROS, but these levels significantly decreased with differentiation.

2017-03-30 | E-MTAB-5438 | biostudies-arrayexpress

A novel CD4+ T cell population expanded in SLE blood provides B cell help through IL10 and succinate

Project description:A novel CD4+ T cell population expanded in SLE blood provides B cell help through IL10 and succinate

| PRJNA487516 | ENA

Gene expression of primary human T Follicular Helper (TFH) cells and naive CD4-positive helper T cells from tonsils of healthy volunteers

Project description:In this experiment we generated Affymetrix gene expression data for T Follicular Helper (TFH) cells from tonsils of healthy volunteers (4 biological replicates) and naive CD4-positive helper T cells (2 biological replicates). TFH cells provide a model relevant to SLE as TFH operate upstream of the activation of pathogenic autoantibody-producing B cells during the disease. This experiment accompanies promoter capture-C and ATAC-seq experiments on the same cell types.

2019-04-01 | E-MTAB-6637 | biostudies-arrayexpress

The CD4+ CD52 low T Cells Contributes to the Development of Systemic Lupus Erythematosus through the CCR8/TARC Pathways

Project description:Objective: CD52 is a cell-surface glycoprotein that is widely expressed in lymphocytes. CD4+CD52high T cells inhibit the activation of CD4+CD52low T cells through the release of cell-surface CD52. The role of the immune regulation of these cells in systemic lupus erythematosus (SLE) is unknown. Methods: Blood samples obtained from SLE patients, rheumatoid arthritis (RA) patients and 33 healthy controls (HC). The expressions of CD4+CD52high T cells and CD4+CD52low T cells were analyzed by flow cytometry. To determine the genetic characteristics of these cells from SLE, we performed cDNA microarrays and examined the function of the genes in in-vitro. Results: The expression of CD4+CD52low T cells in the SLE was significantly higher than HC and non-SLE and its expression were positively correlated with SLEDAI, anti-ds-DNA antibodies and IgG. The population of circulating follicular helper like T cells (Tfh like cells) were increased in SLE and its expression was positively correlated with CD4+CD52low T cells. The microarray analysis revealed that the expression of chemokine receptor 8 (CCR8) is increased in CD4+CD52low T cells. In addition, in vitro experiments using CD4 T cells from patients with SLE showed that thymus and activation-regulated chemokine (TARC), known as a ligand of CCR8, induced the conversion of CD4+CD52high T cells into CD4+CD52low T cells. Conclusion: Our data suggest that increased CD4+CD52low T cells along with increased Tfh like cells are involved in the pathogenic autoantibodies production and that TRAC may contributes to the development of SLE via an aberrant induction of CD4+CD52low T cells.

2017-02-14 | GSE94815 | GEO

A novel CD4 T cell population expanded in SLE blood provides B cell help through IL10 and succinate [ATAC-seq]

Project description:A novel CD4 T cell population expanded in SLE blood provides B cell help through IL10 and succinate [ATAC-seq]

| PRJNA432568 | ENA

ATAC-seq of primary human T Follicular Helper (TFH) cells and naive CD4-positive helper T cells from tonsils of healthy volunteers

Project description:Genome Wide Association Studies (GWAS) have been successful in yielding >60 loci for Systemic Lupus Erythematosus (SLE). However, it is known that GWAS just reports genomic signals and not necessarily the precise localization of culprit genes, with eQTL efforts only able to infer causality to a minority of such loci. Thus, we sought to carry out physical and direct ‘variant to gene mapping’ by integrating results from high-throughput chromatin conformation capture and ATAC-seq assays. This experiment refers to the ATAC-seq part of our work. To determine informative proxy SNPs for each of the SLE GWAS sentinel loci, we generated ATAC-seq open chromatin maps for primary human T Follicular Helper (TFH) cells from tonsils of healthy volunteers (3 biological replicates), a model relevant to SLE as TFH operate upstream of the activation of pathogenic autoantibody-producing B cells during the disease. We also generated open chromatin maps for naive CD4-positive helper T cells (3 biological replicates).

2020-05-12 | E-MTAB-6617 | biostudies-arrayexpress

A novel CD4+ T cell population expanded in Systemic Lupus Erythematosus (SLE) blood provides B cell help through IL10 and succinate

Project description:A novel CD4+ T cell population expanded in Systemic Lupus Erythematosus (SLE) blood provides B cell help through IL10 and succinate

| PRJNA432168 | ENA

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