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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE110017 | GEO | 2018/02/02

REPOSITORIES: GEO

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

Project description: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.

2018-09-26 | GSE118951 | GEO

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

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

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

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

Investigation of gene expression profiles in CD4+ T cells from SLE patients and normal controls

Project description:To investigate the lncRNAs expression profiling in CD4+ T cells of systemic lupus erythematosus (SLE) patients, we have employed “Agilent Human lncRNA 4*180K microarray” as a discovery platform to identify lncRNAs and mRNAs expression signatures in CD4+ T cells between SLE patients and normal controls. CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of peripheral blood in SLE patients and normal controls, respectively.

2021-08-05 | GSE181500 | 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

Transcription profiling of human separated leukocyte subsets in SLE and vasculitis

Project description:Objective: To optimize a strategy for identifying gene expression signatures differentiating SLE and anti-neutrophil cytoplasmic antibody-associated vasculitis that provide insight into the pathogenesis and identify biomarkers.<br/> Methods: Forty four vasculitis patients, 13 SLE patients and 25 age and sex-matched controls were enrolled. CD4 and CD8 T cells, B cells, monocytes and neutrophils were isolated from each patient and, together with unseparated peripheral blood mononuclear cells (PBMC), were hybridised to spotted oligonucleotide microarrays. <br/> Results: Using expression data obtained from purified cells we identified a substantial number of differentially expressed genes that were not detectable in the analysis of PBMC. Analysis of purified T cells identified an SLE-associated, CD4 T cell signature consistent with type 1 interferon signalling driving the generation and survival of tissue homing T cells and thereby contributing to disease pathogenesis. Moreover, hierarchical clustering using expression data from purified monocytes provided significantly improved discrimination between the patient groups than that obtained using PBMC data, presumably because the differentially expressed genes reflect genuine differences in processes underlying disease pathogenesis. <br/> Conclusion: The analysis of leucocyte subsets enabled the identification of gene signatures of both pathogenic relevance and with better disease discrimination than those identified in PBMCs. Thus, this approach provides substantial advantages in the search for diagnostic and prognostic biomarkers in autoimmune disease.

2010-06-02 | E-MTAB-145 | biostudies-arrayexpress

Expression data in PBMCs from SLE patients and controls

Project description:Peripheral blood mononuclear cells were collected from SLE patients in an observational study performed at the University of Michigan Blood microarray expression data were used to confirm the presence of an Interferon signature and identify additional surrogate genes RNA from PBMCs of SLE patients and normal donor controls were obtained for one time point and were profiled on Affymetrix arrays

2015-03-31 | E-GEOD-50772 | biostudies-arrayexpress

SLE lupus RNA-seq

Project description:RNA-seq of systemic lupus erythematosus (SLE) whole blood and healthy controls to determine the gene expression changes in these patients. RNA-seq of PAXgene blood from SLE and healthy donors.

2015-09-16 | E-GEOD-72509 | biostudies-arrayexpress

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