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

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

PROVIDER: PRJNA432168 | ENA |

REPOSITORIES: ENA

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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 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 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

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 in RNP autoantibody+ systemic lupus erythematosus (SLE) patient blood

Project description:The goal of this study was to characterize gene expression profiles in RNP autoantibody+ SLE versus healthy blood donors with a focus on select cytokines that may be important in B cell activation and differentiation, including BAFF, IL-21, and IL-33. We utilized Affymetrix microarrays to characterize the global program of gene expression in the SLE patients, and to identify differentially expressed genes in patients compared to healthy controls. We examined a cohort of 79 consecutive patients classified as anti-ribonuclear protein (anti-RNP)+ systemic lupus erythematosus (SLE). All patients provided RNA samples obtained after providing informed consent. There were 73 female and 6 male subjects. Disease duration ranged from 0 to 453 months with a median of 37.5 months. SLE Disease Activity Index (SLEDAI) ranged from 0 to 31 with a median of 6. mRNA from the blood of a SLE cohort (79 patients with some repeat visits for a total of 99 arrays) and 30 healthy volunteers (one array per volunteer) were analyzed.

2015-01-01 | E-GEOD-61635 | biostudies-arrayexpress

Gene expression in RNP autoantibody+ systemic lupus erythematosus (SLE) patient blood

2015-01-01 | GSE61635 | GEO

miRNAs expression in kidney tissues of systemic lupus erythematosus (SLE) individuals

Project description:MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states, including inflammatory autoimmune diseases. By using high-throughput microRNA profiling analysis, we identified a series of miRNAs dysregulated in local inflammatory lesions of human patients with autoimmune diseases such as SLE. We isolated the renal biopsy samples from eight SLE patients as well as tumor adjacent kidney tissues from four kidney cancer patients as controls for comparison. Total RNA was extracted for the TaqManM-BM-. Low Density Assay v3.0

2012-12-19 | E-GEOD-37426 | biostudies-arrayexpress

Transcriptomic signature in patients with systemic lupus erythematosus (SLE) [T cells]

Project description:T cell abnormalities are well-known features of patients with systemic lupus erythematosus (SLE). The role of CD4 and CD8 T lymphocytes, however, remains poorly understood with data suggesting both protective and deleterious roles. This project aimed to identify a cell-specific transcriptional signature in patients with SLE that could be used as a prognostic disease marker. The overall objective is to correlate the clinical presentation with specific RNA signatures to determine if there are signatures that correlate with disease outcome

2021-02-11 | GSE97263 | GEO

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