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

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

PROVIDER: PRJNA487516 | ENA |

REPOSITORIES: ENA

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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 [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

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

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 CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate.

Project description: Not available

| S-EPMC6325012 | biostudies-literature

Effects of TNFR1 deletion on Il10-/- mouse colitis in early life

Project description:The loss of TNFR1 (Tnfrsf1a) in the Il10-/- spontaneous mouse colitis background results in acceleration of disease onset. Whereas Il10-/- mice on the Bl/6 background are relatively protected from colitis throughout life, Il10-/- Tnfr1-/- mice develop colitis beginning at 4 wks of age. Their disease results in nearly 50% mortality by 12 wks of age. We hypothesized that this early-onset colitis was due to dysregulation of immune signals in early life, defining a key period known as the "weaning reaction" in which proinflammatory signals help induce mucosal tolerance of the microbiome. To test this hypothesis, we profiled, using mRNA-Seq, the colonic transcriptomes from Il10-/- and Il10-/- Tnfr1-/- mice at 2 wks of age. The results presented here show that Il10-/- Tnfr1-/- mice have reduced expression of cytokines at this early age, suggesting that they cannot amount an appropriate immune response. Thus, TNFR1 plays an important role in the weaning reaction and the acquisition of tolerance.

2020-08-04 | GSE155626 | GEO

Ileum/colon treated with succinate

Project description:Ileum/colon treated with succinate

| PRJNA608465 | ENA

Transcriptional profiles of pediatric SLE neutrophils and Healthy neutrophils cultured with SLE sera or Interferon

Project description:Mature neutrophis were freshly isolated from blood of pediatric systemic lupus erythematosus (SLE) patients and healthy donors. Illumina microarray was used to assess transcriptional changes between SLE group and Control group. To uderstand further the gene expression difference between SLE and healthy neutrofils, neutrophils from healthy donors were cultured with autologous sera, SLE sera or Interferon and microarray data was used to compare with fresh SLE neutrophils.

2011-03-10 | GSE27427 | GEO

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