Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA120025 | ENA |
REPOSITORIES: ENA
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Project description:Influence of type I Interferons on function of splenic conventional dendritic cells.
| PRJNA113147 | ENA
Project description:Local and systemic immunosuppression are prominent features of pancreatic cancer, rendering anti-tumor effector cells inactive and immunotherapeutic approaches ineffective. The spleen, an understudied point of antigen-presentation and T cell priming in humans, holds particular importance in pancreatic cancer due to its proximity to the developing tumor. As main effectors of antigen presentation, dendritic cells display antigens to lymphocytes, thereby bridging the innate and adaptive immune response. While tumor-infiltrating anti-inflammatory dendritic cells have been described, splenic dendritic cells have historically just been considered to stimulate the anti-tumor immune response. Here, we describe, for the first time, the presence of an immunosuppressive, tolerogenic IDO1+ dendritic cell subset in the spleens of pancreatic cancer patients that likely contributes to systemic immunosuppression that is associated with pancreatic ductal adenocarcinoma. Network analysis of scRNA seq data reveals extensive communication networks between the identified tolerogenic DC cluster and numerous immune cell populations in the spleen. Interactions with innate and adaptive immune cells suggest a broad influence on leukocyte trafficking and immune regulation within the spleen microenvironment. The identification of signaling pathways involving AHR and IDO-1, CCL19, NECTIN2, CLEC2D, and others elucidates potential mechanisms underlying the immunosuppressive functions of this cell type.
2024-11-14 | GSE247635 | GEO
Project description:Mouse splenic dendritic cells are divided into different subsets based on their phynotype. CD8α+ and CD8α- dendritic cells play different roles against pathogens. Cross-presentation is essential for immune defense against viruses, tumors and intracellular bacteria and CD8α+ DCs are more potent in cross-presentation compared to CD8α- DCs. We used microarrays to detail the global gene expression to analyze the underlying mechanism in CD8α+ dendritic cells cross-presentation Splenic CD8α+ and CD8α- dendritic cells were sorted by flow-cytometer for RNA extraction and hybridization on Affymetrix microarrays. Thirty C57BL/6J mice were sacrified for the splenic cells, splenic DCs were enriched by negtive selection, then CD8α+ and CD8α- dendritic cells were seprated based on CD11c and CD8α markers.
2016-07-27 | E-GEOD-64124 | biostudies-arrayexpress
Project description:We inflicted TBI to wildetype (wt) mice in order to establish whether the anti-inflammatory agent cyclophosphamide can be used therapeutically. Cyclophosphamide was found to regulate distinct inflammatory cells such as activated microglia separate from invading phagocytes and dendritic cells. Cyclophosphamide postinjury selectively reduces antigen-presenting dendritic cells. Findings show feasibility of drug development to interfere with brain inflammation.
2014-06-14 | GSE58484 | GEO
Project description:Gene expression profiles of mouse splenic macrophages and CD8+ and CD8- conventional dendritic cells
| PRJNA143703 | ENA
Project description:Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo we specifically targeted antigens to the two major subsets of DCs using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on MHC class II. This difference in antigen processing is intrinsic to the DC subsets and associated with increased expression of proteins associated with MHC processing. Keywords: cell type comparison of wildtype and Flt3L melonom spleen DCs and splenic B cells, CD4 and CD8 T cells
2006-12-01 | GSE6259 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Immune evasion is an important hallmark of cancer ensured by diverse strategies, including immunosuppression and downregulation of antigen presentation. Here, to restore immunogenicity of cancer cells, we employed the minimal gene regulatory network of highly immunogenic type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen presenting cells (APCs). We showed that enforced expression of PU.1, IRF8 and BATF3 (PIB) was sufficient to induce cDC1 phenotype in 33 cell lines derived from human and mouse hematological and solid tumors. PIB gradually modified the cancer cell transcriptional and epigenetic program imposing global antigen presentation and cDC1 gene signatures within 9 days. cDC1 reprogramming restored the expression of antigen presentation complexes as well as co-stimulatory molecules at the cell surface, leading to the presentation of endogenous antigens on MHC-I, and to CD8+ T cell mediated killing. Functionally, tumor- APCs acquired the ability to uptake and process exogenous proteins and dead cells, secreted inflammatory cytokines and cross-presented antigens to naïve CD8+ T cells. Importantly, tumor-APCs were efficiently generated at the single cell level from primary cancer cells of 7 solid tumors that presented antigens to memory and naïve T-cells, as well as to activated patient-specific intra-tumoral lymphocytes. Alongside antigen presentation, tumor-APCs harboring TP53, KRAS and PTEN mutations showed impaired tumorigenicity in vitro and in vivo. Finally, using in vivo mouse models of melanoma, we showed that intra-tumoral injection of tumor-APCs promoted lymphoid infiltration, delayed tumor growth and increased survival. The anti-tumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors enabling tumor eradication. Our approach combines cDC1’s antigen processing and presenting abilities with endogenous generation of tumor antigens and serves as a platform for the development of novel immunotherapies based on endowed antigen presentation in cancer cells.
2023-10-24 | PXD039789 | Pride