Inflammasomes within hyperactive dendritic cells stimulate T cell mediated anti-tumor immunity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA656938 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12445118_1.fastq.gz | Fastqsanger.gz | |||
| SRR12445118_2.fastq.gz | Fastqsanger.gz | |||
| SRR12445119_1.fastq.gz | Fastqsanger.gz | |||
| SRR12445119_2.fastq.gz | Fastqsanger.gz | |||
| SRR12445120_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 72 |
Similar Datasets
Project description:Central to anti-tumor immunity are dendritic cells (DCs), which can stimulate long-lived protective T cell responses. Recent studies have demonstrated that DCs can achieve a state of hyperactivation, which is associated with inflammasome activities within living cells. Herein, we report that hyperactive DCs have an enhanced ability to migrate to draining lymph nodes and stimulate potent cytotoxic T lymphocyte (CTL) responses. This enhanced migratory activity is dependent on the chemokine receptor CCR7 and is associated with a unique transcriptional program that is not observed in conventionally activated or pyroptotic DCs. We discovered that hyperactivating stimuli are uniquely capable of inducing durable CTL-mediated anti-tumor immunity against tumors that are sensitive or resistant to PD-1 inhibition. These protective responses are intrinsic to the cDC1 subset of DCs, depend on the inflammasome-dependent cytokine IL-1β and enable tumor lysates to serve as immunogens. Therefore, hyperactive DCs may diversify current approaches to cancer immunotherapy.
2020-08-14 | GSE156159 | GEO
Project description:Central to anti-tumor immunity are dendritic cells (DCs), which stimulate long-lived protective T cell responses. Recent studies have demonstrated that DCs can achieve a state of hyperactivation, which is associated with inflammasome activities within living cells. Herein, we report that hyperactive DCs have an enhanced ability to migrate to draining lymph nodes and stimulate potent cytotoxic T lymphocyte (CTL) responses. This enhanced migratory activity is dependent on the chemokine receptor CCR7 and is associated with a unique transcriptional program that is not observed in conventionally activated or pyroptotic DCs. We show that hyperactivating stimuli are uniquely capable of inducing durable CTL-mediated anti-tumor immunity against tumors that are sensitive or resistant to PD-1 inhibition. These protective responses are intrinsic to the cDC1 subset of DCs, depend on the inflammasome-dependent cytokine IL-1?, and enable tumor lysates to serve as immunogens. If these activities are verified in humans, hyperactive DCs may impact immunotherapy.
| S-EPMC7727444 | biostudies-literature
Project description:The adaptor protein ASC contributes to innate immunity through the assembly of caspase-1-activating inflammasome complexes. We demonstrate that ASC plays an inflammasome-independent cell-intrinsic role in adaptive immune cells. Asc-/- mice displayed defective antigen presentation by dendritic cells and lymphocyte migration due to impaired Rac-mediated actin polymerization. Genome-wide analysis showed that ASC, but not Nlrp3 or caspase-1, controls mRNA stability and expression of DOCK2, a guanine nucleotide exchange factor that mediates Rac-dependent signaling in immune cells. DOCK2-deficient dendritic cells showed similar defective antigen uptake as Asc-/- cells. Ectopic expression of DOCK2 in ASC-deficient cells restored Rac-mediated actin polymerization, antigen uptake and chemotaxis. Thus, ASC shapes adaptive immunity independently of inflammasomes by modulating DOCK2-dependent Rac activation and F-actin polymerization in dendritic cells and lymphocytes. Three replicates of naïve WT and three replicates of Asc-/- bone marrow derived dendritic cells were analyzed on the Affymetrix HT MG-430 PM plate array.
2012-07-08 | E-GEOD-30769 | biostudies-arrayexpress
Project description:Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ2= 19.1, df = 2, p = 7.0 x 10-5). Further extensive phenotypic analyses suggest that DUF1220 KO mice are hyperactive (p < 0.05) relative to wild type litter mates. The linking of DUF1220 loss to a hyperactive phenotype is consistent with separate findings in which DUF1220 over expression results in a down-regulation of mitochondrial function, suggesting a possible role in the prolongation of developmental processes (neoteny) that is most pronounced in the human lineage. Total RNA obtained from brain of 3 male homozygous Duf1220 ko and 4 male wildtype mice
2014-09-22 | E-GEOD-58308 | biostudies-arrayexpress
Project description:In this study we developed immunofilaments - nanosized synthetic polymers - for the antigen-specific activation of T cells. Immunofilaments effectively stimulate CD8+ T cells, but it is unclear how well this stimulation compares to natural dendritic cell activation. In this study, we want to investigate the pathways triggered by the immunofilament and the dendritic cell.
2022-10-14 | GSE215208 | GEO
Project description:The adaptor protein ASC contributes to innate immunity through the assembly of caspase-1-activating inflammasome complexes. We demonstrate that ASC plays an inflammasome-independent cell-intrinsic role in adaptive immune cells. Asc-/- mice displayed defective antigen presentation by dendritic cells and lymphocyte migration due to impaired Rac-mediated actin polymerization. Genome-wide analysis showed that ASC, but not Nlrp3 or caspase-1, controls mRNA stability and expression of DOCK2, a guanine nucleotide exchange factor that mediates Rac-dependent signaling in immune cells. DOCK2-deficient dendritic cells showed similar defective antigen uptake as Asc-/- cells. Ectopic expression of DOCK2 in ASC-deficient cells restored Rac-mediated actin polymerization, antigen uptake and chemotaxis. Thus, ASC shapes adaptive immunity independently of inflammasomes by modulating DOCK2-dependent Rac activation and F-actin polymerization in dendritic cells and lymphocytes.
2012-07-09 | GSE30769 | GEO
Project description:Hyperactive PI3K-delta in Th1 and Th2 differentiation
| PRJNA887433 | ENA
Project description:Hyperactive RAS/MAPK introduces cancer-specific mitotic vulnerabilities
| PRJNA723590 | ENA
Project description:Langerhans Cell Histiocytosis (LCH) is an inflammatory disease characterized by abnormal dendritic cells (DCs) with hyperactive ERK signaling, called “LCH cells”. Since DCs rely on ERK signaling to produce inflammatory signaling molecules in response to pathogenic cues, we hypothesized that hyperactive ERK will enhance DC inflammatory responses. We utilized the BRAF-V600E fl/+: CD11c-Cre mouse model of LCH which hyperactivates MAPK/ERK signaling in DCs. We cultured bone-marrow derived dendritic cells (BMDCs) from LCH and control mice (BRAF-V600E fl/+: Cre0) and stimulated them with LPS with or without a specific BRAF-V600E inhibitor. Polysome Profiling revealed a large and irreversible increase in levels of polysome bound RNA in the LCH-BMDCs compared to WT. We defined the LCH translatome by analyzing total and polysome-bound RNA from BMDCs using the Anota2seq program, which revealed a BRAF-V600E-mediated selective increase in LPS-induced inflammatory proteins.
2022-05-01 | GSE193610 | GEO
Project description:Sequences encoding DUF1220 protein domains show the most extreme human lineage-specific copy number increase of any coding region in the genome and have been linked to human brain evolution. In addition, DUF1220 copy number (dosage) has been implicated in influencing brain size within the human species, both in normal populations and in individuals associated with brain size pathologies (1q21-associated microcephaly and macrocephaly). More recently, increasing dosage of a subtype of DUF1220 has been linked with increasing severity of the primary symptoms of autism. Despite these intriguing associations, a function for these domains has not been described. As a first step in addressing this question we have developed the first transgenic model of DUF1220 function by removing the single DUF1220 domain (the ancestral form) encoded in the mouse genome. While resulting DUF1220-minus (KO) mice show no obvious anatomical peculiarities, they exhibit a significantly reduced fecundity (χ2= 19.1, df = 2, p = 7.0 x 10-5). Further extensive phenotypic analyses suggest that DUF1220 KO mice are hyperactive (p < 0.05) relative to wild type litter mates. The linking of DUF1220 loss to a hyperactive phenotype is consistent with separate findings in which DUF1220 over expression results in a down-regulation of mitochondrial function, suggesting a possible role in the prolongation of developmental processes (neoteny) that is most pronounced in the human lineage.
2014-09-22 | GSE58308 | GEO