Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glycolysis Promotes Phosphoinositide 3-Kinase Signaling In Support of T Helper 17 Cell-Mediated Autoimmunity

ABSTRACT: Glycolysis Promotes Phosphoinositide 3-Kinase Signaling In Support of T Helper 17 Cell-Mediated Autoimmunity

PROVIDER: PRJNA692622 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Glycolysis Promotes Phosphoinositide 3-Kinase Signaling In Support of T Helper 17 Cell-Mediated Autoimmunity

Project description:T helper (Th) cell differentiation is driven by antigen and accessory signals that activate phosphoinositide 3-kinase (PI3K) to induce transcriptional and metabolic reprogramming including aerobic glycolysis (the Warburg effect). Here, we show that ATP generated through glycolysis fuels PI3K signaling to promote pathogenic Th17 cell responses. Mice with T cell-specific ablation of the glycolytic enzyme lactate dehydrogenase A (LDHA) were resistant to Th17 cell-mediated experimental autoimmune encephalomyelitis in association with defective T cell activation, migration, proliferation, and differentiation. LDHA deficiency crippled the cellular redox balance and inhibited ATP production causing attenuated phosphoinositide (3,4,5)-trisphosphate generation, and diminished activation of the Akt kinase and phosphorylation of its transcription factor target Foxo1. Th17 cell-specific expression of an Akt-insensitive Foxo1 mutant recapitulated the Th17 cell differentiation defects caused by LDHA deficiency. Thus, PI3K signaling and glycolytic bioenergetics constitute a positive feedback regulatory circuit essential for Th17 cell-mediated autoimmunity.

2021-03-27 | GSE164959 | GEO

Low affinity TCRs support regulatory T cell function in autoimmunity

Project description:Low affinity TCRs support regulatory T cell function in autoimmunity

| PRJNA416932 | ENA

B Cells Polarize Pathogenic Inflammatory T Helper Subsets through ICOSL-Dependent Glycolysis

Project description:B Cells Polarize Pathogenic Inflammatory T Helper Subsets through ICOSL-Dependent Glycolysis

| PRJNA603415 | ENA

B Cells Polarize Pathogenic Inflammatory T Helper Subsets through ICOSL-Dependent Glycolysis

Project description:B cells constitute abundant cellular components in inflamed human tissues, but their role in pathogenesis of inflammatory T helper (Th) subsets is still unclear. Here, we demonstrate that B cells, particularly resting naïve B cells, have a previously unrecognized helper function that is involved in shaping the metabolic process and subsequent inflammatory differentiation of T-cell-receptor-primed Th cells. ICOS/ICOSL axis-mediated glucose incorporation and utilization were crucial for inflammatory Th subset induction by B cells, and activation of mTOR was critical for T cell glycolysis in this process. Consistently, upon encountering ICOSL+ B cells, activated effector memory Th cells from patients with rheumatoid arthritis or systemic lupus erythematosus spontaneously differentiated into inflammatory Th subsets. Immunotherapy using an anti-CD20 antibody that specifically depleted B cells in patients with rheumatoid arthritis efficiently abrogated the capabilities of memory Th cells to incorporate and utilize glucose, thereby impairing the pathogenic differentiation of inflammatory Th subsets. To examine the metabolic process of Th cells after interacting with autologous B cells, we applied RNA-sequencing to analyze their transcriptional profiles.

2022-06-30 | GSE144339 | GEO

PD-L1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS IN CANCER, ALLERGY AND AUTOIMMUNITY

Project description:In this study, we define a novel phenotypic and functional dichotomy of human dendritic cells (DC), with strong relevance to cancer, allergy, and autoimmunity. Using 16 different stimuli in vitro (130 observations), we describe two states of human activated DC. PD-L1highICOSLlow Secretory DC produced large amounts of inflammatory cytokines and chemokines but induced very low levels of T helper (Th) cytokines following DC-T co-culture; conversely PD-L1lowICOSLhigh Helper DC produced low levels of secreted factors but induced high levels and a broad range of Th cytokines. Secretory DC were aligned with mature migratory LAMP3+ DC in three different cancer types, atopic dermatitis, and lupus nephritis by single-cell transcriptomics. They were associated with T cell inflammation, overexpressed stimulatory and inhibitory checkpoints, acquired increased cell-cell communication, and were associated with good prognosis in head and neck squamous cell carcinoma, and with response to checkpoint blockade in Melanoma. This functional dichotomy of DC has broad implications in inflammation and immunotherapy.

2022-01-01 | GSE169381 | GEO

PD-L1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS IN CANCER, ALLERGY AND AUTOIMMUNITY [CITE-seq]

2022-01-01 | GSE170673 | GEO

Skin and gut imprinted T helper cell subsets exhibit distinct functional phenotypes in CNS autoimmunity

Project description:Skin and gut imprinted T helper cell subsets exhibit distinct functional phenotypes in CNS autoimmunity

| PRJNA718463 | ENA

Stool metaproteomics of children with islet autoimmunity

Project description:The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. Here, we apply an integrative approach to combine comprehensive faecal virome, microbiome and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children. We show strong age and antibody related effects across the datasets. Mastadenovirus infection was associated with profound functional changes in the faecal metaproteome. Multiomic factor analysis modelling revealed proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. These findings demonstrate functional remodelling of the gut microbiota accompanies both islet autoimmunity and viral infection.

2022-08-22 | PXD032997 | Pride

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

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

| PRJNA557414 | ENA

PD-L1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS IN CANCER, ALLERGY AND AUTOIMMUNITY

Project description:PD-L1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS IN CANCER, ALLERGY AND AUTOIMMUNITY

| PRJNA716347 | ENA