Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Follicular helper T cells enhance autoimmunity through Ascl-2 in a murine model for Sjögren’s syndrome

ABSTRACT: We investigated how Tfh cells contribute to the breakdown of peripheral immune tolerance and the formation of autoimmune lesions in a murine model of SS. Our results indicate a yet unreported mechanism of autoreactive response through Tfh cells in a SS model mouse, and it will be supportive for understanding the pathogenesis of autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE123332 | GEO | 2018/12/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

CXCR5+PD-1+CD8+ T cells are a novel T helper cell sublineage and are negatively regulated by Stat5 [scRNA-Seq]

Project description:Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ Tfh cells are the main subset regulating autoreactive B cells. Here, we discover a distinct novel CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively regulated by Stat5. These CD8+ Tfh cells regulate the GC B cell response and control autoantibody production. Deficiency of Stat5 in CD8+ T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and autoantibody production. CD8+ Tfh share similar gene signatures with CD4+ Tfh and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance

2019-08-30 | GSE136641 | GEO

CXCR5+PD-1+CD8+ T cells are a distinct sublineage of CD8+ Tfh cells and Stat5 suppresses the expression of the Tfh-specific genes in CXCR5+PD-1+CD8+ T cells [RNA-Seq]

Project description:Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ Tfh cells are the main subset regulating autoreactive B cells. Here, we discover a novel CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively regulated by Stat5. These CD8+ Tfh cells regulate the GC B cell response and control autoantibody production. Deficiency of Stat5 in CD8+ T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and autoantibody production. CD8+ Tfh cells share similar gene signatures with CD4+ Tfh cells and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance

2019-08-30 | GSE136640 | GEO

Store-operated Ca2+ entry in follicular T cells controls humoral immune responses and autoimmunity

Project description:T follicular helper (TFH) cells promote affinity maturation of B cells in germinal centers (GCs), whereas T follicular regulatory (TFR) cells limit GC reaction. Store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels mediated by STIM and ORAI proteins is a fundamental signaling pathway in T lymphocytes. Here we show that SOCE is required for the differentiation and function of both TFH and TFR cells. Conditional deletion of Stim1 and Stim2 genes in T cells or Treg cells results in spontaneous autoantibody production and humoral autoimmunity. Conversely, antibody-mediated immune responses following viral infection critically depend on SOCE in TFH cells. Mechanistically, STIM1 and STIM2 control early TFR and TFH cell differentiation through NFAT-mediated IRF4, BATF and Bcl-6 expression. SOCE plays a dual role in GC response by controlling TFH and TFR cell function, thus enabling protective B cell responses and preventing humoral autoimmunity. RNAseq analyses of WT and Stim1Stim2 DKO follicular T cells and non-follicular T cells; 4-6 mice per cohort in duplicates. Mice were infected for 10 days with LCMV.

2016-03-10 | E-GEOD-79039 | biostudies-arrayexpress

Store-operated Ca2+ entry in follicular T cells controls humoral immune responses and autoimmunity

2016-03-10 | GSE79039 | GEO

Bach2 deficiency leads to spontaneous expansion of IL-4-producing T follicular helper cells and autoimmunity

Project description:The transcription factor Bach2 is a critical negative regulator of Tfh cell differentiation, especially IL-4 subset. Tfh cells from the mesenteric lymph nodes of WT and Bach2 CD4 conditional KO mice were collected to process the Rna-seq. Mechanistically, Bach2 may limit abnormal IL-4-produicng Tfh cell formation by repressing c-Maf, CXCR5 and IL-4.

2021-01-26 | GSE135087 | GEO

Quantitative Analysis of Global Proteome and Lysine Acetylome for Human CD4+ T Follicular Helper Cells

Project description:Follicular helper T (Tfh) are a subset of CD4+ T helper cells that provide help to germinal center B cells and mediate the development of long-lived humoral immunity. Tfh cells dysregulation is associated with several major autoimmune diseases. Although recent studies showed Tfh cells differentiation is controlled by the transcription factor Bcl6, cytokines and cell-cell signals, limited information is available on the proteome and post-translational modifications (PTM) of proteins in human Tfh cells. In this study, using TMT labeling technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome and acetylome in human naive CD4+ T cells and in vitro induced Tfh (iTfh) cells. In total, we identified 802 up-regulated proteins and 598 down-regulated proteins at the threshold of 1.5 folds in iTfh cells compared to naive CD4+ T cells. With the aid of intensive bioinformatics, biological process, cellular compartment, molecular function, KEGG pathway and protein-protein interaction of these differentially expressed proteins were revealed. Moreover, our acetylome data showed that 22 lysine acetylated proteins are up-regulated and 26 lysine acetylated proteins are down-regulated in iTfh cells compared to the naive CD4+ T cells, among which 11 differentially acetylated lysine residues in core histone were identified, indicating proteins acetylation and epigenetic mechanism are involved in regulating Tfh cells differentiation. These data provide a significant resource for studies of Tfh differentiation and normal and perturbed Tfh cell function.

2021-03-19 | PXD008563 | Pride

Follicular helper T cells express a metabolic and cell signaling gene signature in a lupus-prone murine model

Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease in which autoreactive follicular helper T (Tfh) cells license high-affinity autoantibody production. Strikingly, the frequency of circulating Tfh is correlated with disease activity in SLE patients. As such, understanding the molecular mechanisms responsible for the aberrant Tfh cell generation and activation in lupus is of fundamental significance. We previously demonstrated that expanded Tfh cells in the B6.Sle1.Sle2.Sle3 (TC for triple congenic) lupus model exhibit high glycolysis and oxidative metabolism, which can be constrained by inhibiting glycolysis with 2-deoxyglucose (2DG). We performed RNA-seq analyses of splenic Tfh and naïve CD4+ T cells (Tn) comparing between TC and B6 mice. First, data revealed a large number of shared gene signatures in Tfh and Tn comparing between TC and B6 group, implicating that the aberrant development of Tfh initiates as early as Tn state. Further alignment of the Tfh transcriptome obtained from RNA-seq and earlier microarray assays demonstrated concerted alterations in numerous gene signatures of overactivation of T cells including dysregulated tyrosine kinase signaling and MAPK signaling pathways. Gene set enrichment analyses (GSEA) further revealed altered metabolic pathways (e.g., oxidative phosphorylation and pyruvate metabolism) among splenic TC Tfh cells.

2021-09-01 | GSE157648 | GEO

Gel-Free Proteomics of Sjögren’s Syndrome patient saliva

Project description:Sjögren's Syndrome (SS) is an autoimmune exocrinopathy characterized by the progressive damage of salivary and lacrimal glands associated with lymphocytic infiltration. It can be defined as primary SS (pSS) or associated/secondary SS (sSS) if combined with another systemic autoimmune disease. Identifying new non-invasive biomarkers for SS diagnosis remains a challenge, and alterations in saliva composition reported in patients turn this fluid into a source of potential biomarkers. To examine the overall panorama of proteins in saliva, samples of control, pSS, and sSS individuals were analyzed by gel-free LC-MS/MS.

2021-06-09 | PXD025434 | Pride

Gel-based proteomics of Sjögren’s Syndrome patient saliva

2021-06-09 | PXD025463 | Pride

Expression data of T follicular helper cells (Tfh) from follicular lymphoma lymph nodes (FL) or non malignant tonsils (TONS)

Project description:GEP on Affymetrix U133+2.0 microarrays was performed on ex vivo cell-sorted Tfh from FL or TONS GEP was performed on 7 Tfh from FL and 7 Tfh from TONS

2015-02-28 | E-GEOD-66384 | biostudies-arrayexpress

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