Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-MTAB-901
PROVIDER: PRJNA149569 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as “damage-associated molecular patterns” or “alarmins”, remains ill-defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8+ T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a MyD88-dependent, CTL-intrinsic fashion, determined polyfunctional effector cell differentiation and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses. 2 groups (wt vs. ST-/- P14 cells), 3 replicates per group.
2012-02-27 | E-GEOD-34392 | biostudies-arrayexpress
Project description:Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as “damage-associated molecular patterns” or “alarmins”, remains ill-defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8+ T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a MyD88-dependent, CTL-intrinsic fashion, determined polyfunctional effector cell differentiation and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses.
2012-02-27 | GSE34392 | GEO
Project description:The pleiotropic alarmin interleukin-33 (IL-33) promotes the activity of many innate and adaptive immune cell subsets. Its receptor ST2 is constitutively expressed at high levels by type 2-biased immune cells including CD4+ T helper 2 (Th2) cells, innate lymphoid cells type 2 and highly potent regulatory T cells, allowing rapid sensing of IL-33 alarmin signals (Peine et al., 2015). In contrast, during viral infections, antiviral CD8+ cytotoxic T cells (CTLs) and CD4+ Th1 cells express ST2 at a low level in a transient and activation dependent way, suggesting that the ST2-coding gene Il1rl1 is regulated in a cell-type specific manner (Bonilla et al., 2012). To better understand the transcriptional regulation of the Il1rl1 gene in distinctly polarized T cells, we here performed RNA-Sequencing of in vitro activated, ST2 expressing CTLs, Th1 and Th2 cells.
2023-10-17 | GSE204692 | GEO
Project description:Effective cancer immunotherapy requires potent tumor antigen-specific effector CD8+ T cell (CTLeff) responses, culminating in an inflammatory activation of the tumor microenvironment. We describe the artificial reengineering of the lymphocytic choriomeningitis virus (LCMV) genome to serve as replication-competent but stably attenuated immunotherapy platform (artLCMV). artLCMV targeted dendritic cells, thereby delivering tumor-associated antigens for efficient CTL induction. Additionally, owing to in vivo spread, artLCMV infected lymphoid tissue stroma expressing interleukin-33, an alarmin released from necrotic cells. Interleukin-33 signals accounted for artLCMV-induced effector CTL responses of higher magnitude and functionality than those induced by replication-deficient LCMV-, adenovirus 5- or vaccinia virus-based vectors. Accordingly, superior immunotherapeutic efficacy of artLCMV in transplantable tumor models depended on interleukin-33 signaling, and massive CTLeff influx was associated with an inflammatory conversion of the tumor. These properties, together with low seroprevalence but excellent immunogenicity of LCMV in humans, suggest artLCMV holds promise as a cancer immunotherapy platform.
2017-03-08 | GSE84039 | GEO
Project description:T-cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these memory-like CD8 T cell (CD8ML) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection we identify the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8ML as well as for virus control. IL-33 receptor- (ST2-) deficient CD8 T cells exhibit biased end-differentiation and premature loss of Tcf-1. Intriguingly, ST2-deficient CD8ML responses are restored by blockade of type I interferon signaling, suggesting that opposing IFN-I and IL-33 effects control CD8ML formation in chronic infection. IL-33 signals broadly augment chromatin accessibility in CD8ML and determine these cells’ re-expansion potential. Our study identifies the IL-33 – ST2 axis as an important CD8ML-promoting pathway in the context of chronic viral infection.
2023-04-06 | GSE210538 | GEO
Project description:T-cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these memory-like CD8 T cell (CD8ML) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection we identify the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8ML as well as for virus control. IL-33 receptor- (ST2-) deficient CD8 T cells exhibit biased end-differentiation and premature loss of Tcf-1. Intriguingly, ST2-deficient CD8ML responses are restored by blockade of type I interferon signaling, suggesting that opposing IFN-I and IL-33 effects control CD8ML formation in chronic infection. IL-33 signals broadly augment chromatin accessibility in CD8ML and determine these cells’ re-expansion potential. Our study identifies the IL-33 – ST2 axis as an important CD8ML-promoting pathway in the context of chronic viral infection.
2023-04-06 | GSE210537 | GEO
Project description:T-cell factor 1 (Tcf-1) expressing CD8 T cells exhibit stem-like self-renewing capacity rendering them key for immune defense against chronic viral infection and cancer. Yet, the signals that promote the formation and maintenance of these memory-like CD8 T cell (CD8ML) remain poorly defined. Studying CD8 T cell differentiation in mice with chronic viral infection we identify the alarmin interleukin-33 (IL-33) as pivotal for the expansion and stem-like functioning of CD8ML as well as for virus control. IL-33 receptor- (ST2-) deficient CD8 T cells exhibit biased end-differentiation and premature loss of Tcf-1. Intriguingly, ST2-deficient CD8ML responses are restored by blockade of type I interferon signaling, suggesting that opposing IFN-I and IL-33 effects control CD8ML formation in chronic infection. IL-33 signals broadly augment chromatin accessibility in CD8ML and determine these cells’ re-expansion potential. Our study identifies the IL-33 – ST2 axis as an important CD8ML-promoting pathway in the context of chronic viral infection.
2023-04-06 | GSE210536 | GEO
Project description:The cytokine interleukin-33 (IL-33) is an epithelial alarmin with critical roles in allergic inflammation and type 2 immunity. The project aims at the characterization of the direct cleavage of IL-33 by allergen proteases, resulting in its activation, and in the subsequent induction of type 2 cytokine production in group 2 innate lymphoid cells. The present dataset contains mass spectrometry analyses to map the cleavage sites for 9 distinct allergens proteases in the human IL-33 sequence.
2018-03-14 | PXD006081 | Pride
Project description:The pleiotropic alarmin interleukin-33 (IL-33) promotes the activity of many innate and adaptive immune cell subsets. Its receptor ST2 is constitutively expressed at high levels by type 2-biased immune cells including CD4+ T helper 2 (Th2) cells, innate lymphoid cells type 2 and highly potent regulatory T cells, allowing rapid sensing of IL-33 alarmin signals (Peine et al., 2015). In contrast, during viral infections, antiviral CD8+ cytotoxic T cells (CTLs) and CD4+ Th1 cells express ST2 at a low level in a transient and activation dependent way, suggesting that the ST2-coding gene Il1rl1 is regulated in a cell-type specific manner (Bonilla et al., 2012). To better understand the transcriptional regulation of the Il1rl1 gene in distinctly polarized T cells, we here performed RNA-Sequencing of in vitro activated, ST2 expressing CTLs, Th1 and Th2 cells. Further, to decipher the T cell subset-specific consequences of IL-33 sensing, we profiled early changes in transcriptional activity of CTLs, Th1 cells and Th2 cells upon stimulation with IL-33. Lastly, to better understand the role of IL-33 during an acute infection with lymphocytic choriomeningitis virus (LCMV), activated CD44+ CTLs were flowcytometrically sorted from infected C57BL/6 wildtype and Il1rl1 gene-targeted mice (Il1rl1-ExAB-/-) and subjected to combined single-cell gene expression and single cell TCR-Seq analysis. This SuperSeries is composed of the SubSeries listed below.
2023-10-17 | GSE204695 | GEO
Project description:Hereditary sensory and autonomic neuropathy type I (HSAN-I) is neurological disorder characterized by distal sensory neuron dysfunction, frequent infections, and ulcerative mutilations. It remains unknown if HSAN-I directly dampens protective immunity. Here we report that HSAN-I-causing mutations of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) affect human T cell responses. T cell antigenic stimulation and inflammation induce SPTLC2 expression. Murine T cell-specific ablation of Sptlc2 fundamentally impairs antiviral T cell survival and effector function. Mechanistically, SPTLC2-deficiency reduces sphingolipid biosynthetic flux and causes a prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress and CD8+ T cell death. Antiviral CD8+ T cell responses are restored by supplementing sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Our study reveals that SPTLC2 underpins protective adaptive immunity by translating extracellular stimuli into intracellular anabolic signals and reducing cellular stress to maintain metabolic reprogramming sustainability
2019-04-02 | GSE112715 | GEO