Role of activated PI3K-delta signaling in humoral immunity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA720927 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We are examining the consequences of activating mutations in PI3K-delta in Th1 vs. Th2 differentiation. Using the house dust mite (HDM) model of allergic airway inflammation, which drives potent Th2 responses in vivo, we have found mice expressing hyper-activated PI3K-delta show impaired Th2 differentiation and instead favor Th1 cell differentiation. We would like to further investigate this aberrant CD4 differentiation profile using scRNA-seq to characterize PI3K-delta regulated aspects of type II immunity.
2023-10-04 | GSE214871 | GEO
Project description:We report the high-throughput profiling of murine naive B cells, germinal center (dark zone and light zone) B cells, and plasma cells transcriptome. By obtaining over 5 million bases of sequence, we generated genome-wide expression maps of cell subsets from WT mice and aPIK3CD mice. We find that activated PIK3CD signaling lead to significant alteration in gene expression of plasma cells.
2021-09-16 | GSE171795 | GEO
Project description:Cytidine diphosphate (CDP)-ethanolamine pathway of phospholipid metabolism coordinates metabolic programming of Tfh cell responses and humoral immunity.
2021-05-26 | GSE147190 | GEO
Project description:Immune cells can metabolize fatty acids (FAs) to generate energy. The source of different fatty acid species, and their impacts on humoral immunity remains poorly understood. Here we report that proliferating B cells require increased amount of monounsaturated fatty acids (MUFA) to maintain mitochondrial metabolism and mTOR activity, and to prevent excessive autophagy and endoplasmic reticular (ER) stress. Furthermore, B cell extrinsic Stearoyl-Coa desaturase (SCD) activity generates endogenous MUFA to support early B cell development and germinal center (GC) formation in vivo during immunization and influenza infection. Thus, SCD-mediated MUFA production is critical for humoral immunity.
2020-12-02 | GSE162460 | GEO
Project description:Metabolic control of Tfh and humoral immunity by phosphatidylethanolamine
| PRJNA613290 | ENA
Project description:The transcription factor Pax5 is known to control B-cell development, but its role in mature B- cells is largely enigmatic. Here, we demonstrate by conditional mutagenesis in peripheral B- lymphocytes that B-1a, marginal zone (MZ) and germinal center B-cells as well as plasma cells are not generated upon loss of Pax5. Follicular (FO) B-cells tolerate the loss of Pax5 but have a shortened half-life. The Pax5-deficient FO B-cells fail to proliferate upon B-cell receptor or Toll- like receptor stimulation due to impaired PI3K-AKT signaling, which is caused by increased expression of PTEN, a negative regulator of the PI3K pathway. Pax5 restrains PTEN protein expression at the posttranscriptional level, likely involving Pten-targeting microRNAs. Additional PTEN loss in Pten,Pax5 double-mutant mice rescues FO B-cell numbers and the development of MZ B-cells. Hence, the posttranscriptional downregulation of PTEN expression is a dominant function of Pax5 that facilitates the differentiation and survival of mature B cells, thereby promoting humoral immunity.
2021-06-14 | GSE103260 | GEO
Project description:The function of mitochondrial respiration during B cell fate decisions and differentiation 55 remained equivocal. This study reveals that selection for mitochondrial fitness occurs during B 56 cell activation and is essential for subsequent plasma cell differentiation. By expressing a 57 mutated mitochondrial helicase in transitional B cells, we depleted mitochondrial DNA during 58 B cell maturation, resulting in reduced oxidative phosphorylation. Although no changes in 59 follicular B cell development were evident, germinal centers, class switch recombination to 60 IgG, plasma cell maturation and humoral immunity were diminished. Defective oxidative 61 phosphorylation led to aberrant flux of the tricarboxylic acid cycle and lowered the amount of 62 saturated phosphatidic acid. Consequently, mTOR activity and BLIMP1 induction were 63 curtailed whereas HIF1 _and glycolysis were amplified. Exogenous phosphatidic acid 64 increased mTOR activity in activated B cells. Hence, mitochondrial function is required and 65 selected for in activated B cells for the successful generation of functional plasma cells.
2022-04-06 | ST002140 | MetabolomicsWorkbench
Project description:Stearoyl-CoA desaturase mediated monounsaturated fatty acid availability supports humoral immunity
| PRJNA681897 | ENA
Project description:Tumor-associated macrophages (TAMs) are involved in the pathogenesis of Hodgkin lymphoma (HL) and correlate with negative prognosis. The phosphatidylinositol 3-kinase (PI3K) mediates tumor and endothelial cell survival, and macrophage activation. As PI3Kδ and PI3Kγ are constitutively activated in HL, we describe RP6530, a novel PI3Kδ/γ inhibitor, in clinical development for HL and NHL. RP6530 exhibits anti-proliferative and cytotoxic activity both in vitro in HL cell lines and in vivo in HL xenograft mouse models. By inhibiting the metabolic regulator Pyruvate Kinase M2 (PKM2), RP6530 downregulates lactic acid metabolism in HL cells switching the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state. RP6530 reshapes the tumor microenvironment (TME), through the re-polarization of TAMs into pro-inflammatory macrophages and the inhibition of tumor vasculature. These data demonstrate the central role of PI3K δ/γ inhibition for targeting HL cells and TME, indicating RP6530 as a novel therapeutic opportunity for HL patients.
2020-09-07 | GSE105439 | GEO
Project description:Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT) but how this affects immune responses broadly remains unknown. Using a preclinical model of cytomegalovirus (CMV) reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells resulting in sustained IFN secretion which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for immunoglobulin G (IgG) recycling, and rapid IgG loss. In contrast, recipient IgG producing cells are rapidly eliminated after BMT. T cell-specific deletion of IL-6R led to persistence of recipient-derived CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invokes IFN-dependent EC injury and consequent IgG loss leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury thereby preserving humoral immunity after immunotherapy.
2024-04-01 | GSE252180 | GEO