Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA287293 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Dendritic cells (DCs) play a pivotal role in the regulation of the immune response. DC development and activation is finely orchestrated through transcriptional programs. GATA1 transcription factor is required for murine DC development and data suggests that it might be involved in the fine-tuning of the life span and function of activated DCs. We generated DC-specific Gata1 knockout mice (Gata1-KODC), which presented a 20% reduction of splenic DCs, partially explained by enhanced apoptosis. RNA-Seq analysis revealed a number of deregulated genes involved in cell survival, migration and function. DC migration towards peripheral lymph nodes was impaired in Gata1-KODC mice. Migration assays performed in vitro showed that this defect was selective for CCL21, but not CCL19. Interestingly, we show that Gata1-KODC DCs have reduced polysialic acid levels on their surface, which is a known determinant for the proper migration of DCs towards CCL21.
2016-11-08 | GSE69969 | GEO
Project description:<p>We employed next-generation sequencing to identify somatic alterations in multiple metastatic sites from an "exceptional responder" lung adenocarcinoma patient during his seven year course of ERBB2-directed therapies. The degree of heterogeneity was unprecedented, with ~1% similarity between somatic alterations of the lung and lymph nodes. One novel translocation, PLAG1-ACTA2, present in both sites, up-regulated ACTA2 expression. ERBB2, the predominant driver oncogene, was amplified in both sites, more pronounced in the lung, and harbored an L869R mutation in the lymph node. Functional studies demonstrated increased proliferation, migration, metastasis, and resistance to ERBB2-directed therapy due to L869R mutation and increased migration due to ACTA2 overexpression. Within the lung, a nonfunctional CDK12, due to a novel G879V mutation, correlated with down-regulation of DNA damage response genes, causing genomic instability, and sensitivity to chemotherapy. We propose a model whereby a sub-clone metastasized early from the primary site and evolved independently in lymph nodes.</p>
| phs001159 | dbGaP
Project description:Tumors induce tolerance towards their antigens by producing the chemokine CCL21, leading to the formation of tertiary lymphoid organs (TLOs). Ins2-CCL21 transgenic, non-obese diabetic (NOD) mice express CCL21 in pancreatic β-cells and do not develop autoimmune diabetes. We investigated by which mechanisms CCL21 expression prevented diabetes. Islet infiltrates of 4 week-old Ins2-CCL21 mice were enriched in naïve CD4+ T cells and compartmentalized within networks of CD45- gp38+ CD31- fibroblastic reticular cell (FRC)-like stromal cells. Importantly, 12 week-old Ins2-CCL21 NOD islets contained FRC-like cells with enhanced expression of β-cell autoantigens and gene expression profiles consistent with regulatory, anti-inflammatory properties and increased contractility. Consistently, transgenic mice harbored fewer autoreactive T cells and higher proportion of Tregs in the islets. Using adoptive transfer and islet transplantation models, we demonstrate that the formation of TLOs in Ins2-CCL21 transgenic islets is critical for regulation of autoimmunity and while the effect is systemic, the induction may be mediated locally by lymphocyte trafficking through TLOs. Overall, our findings suggest that CCL21 promotes TLOs that differ from inflammatory TLOs associated with islets in T1D in that they resemble lymph nodes, contain FRC-like cells expressing β-cell autoantigens and are able to induce systemic and antigen-specific tolerance leading to diabetes prevention. These findings suggest that CCL21 may be exploited for novel immunoregulation approaches to treat autoimmune diabetes.
2019-09-23 | GSE130979 | GEO
Project description:The capacity of dendritic cells (DC) to migrate from peripheral organs to lymph nodes (LN) is an important event in the initiation of a T cell-mediated immune response. Previously it was shown that the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the 2 multidrug resistance protein 1 (MRP1; ABCC1) play a role in both human and murine DC migration. Here we show that a more recently discovered family-member, MRP4 (ABCC4) is expressed on both epidermal and dermal human skin DC and contributes to the migratory capacity of DC. Pharmacological inhibition of MRP4 activity or down-regulation through RNAi in DC resulted in reduced migration of DC from human skin explants and of in vitro generated Langerhans cells. The responsible MRP4 substrate remains to be identified as exogenous addition of MRP4’s known substrates PGE2, leukotriene B4 and D4 or cyclic nucleotides (all previously implicated in DC migration) could not restore migration. This notwithstanding, our data show that MRP4 is an important molecule, significantly contributing to human DC migration towards the draining lymph nodes, and thereby relevant for the initiation of an immune response and a possible target for immunotherapy. Keywords: cell type comparison, RNAi knockdown for MRP4 2 samples were analyzed to compare. Immature DC cultured from MUTZ3 (reference control) or from MUTZ3-shMRP4 cells
2008-07-12 | E-GEOD-12089 | biostudies-arrayexpress
Project description:Chemokines and adhesion molecules upregulated in lymphatic endothelial cells (LECs) during tissue inflammation are believed to enhance dendritic cell (DC) migration to draining lymph nodes (dLNs), but the in vivo control of this process is not well understood. By performing transcriptional profiling of LECs isolated from murine skin, we found that inflammation induced by a contact hypersensitivity (CHS) response upregulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines in LECs. Furthermore, lymphatic lineage markers like Prox-1, VEGFR3 and LYVE-1 were significantly downregulated during CHS. By contrast, skin inflammation induced by Complete FreundM-bM-^@M-^Ys adjuvant (CFA) induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. In FITC painting experiments, DC migration to dLNs was more strongly increased in CFA- as compared to CHS-induced inflammation. Interestingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 in LECs. However, the requirement for CCR7 signaling became further pronounced during inflammation, whereas CCR7-independent signals only had a minor role in enhancing DC migration. Collectively, these findings indicate that inflammation-induced DC migration is stimulus-dependent and only moderately enhanced by LEC-induced genes other than CCL21. Mouse ear skin single-cell suspensions were prepared by a fast protocol that minimizes the RNA degradation. Fluorescence-activated cell sorting (FACS) was used to sort lymphatic endothelial cells (LEC) from CHS inflammed and control skin. 4 pairs (each with one control and one CHS inflammed sample, sorted and extracted on the same day) of LECs were chosen based on the quality of extracted and amplified material. This gave 8 samples to analyze (4 biological replicates in each condition). Each sample was sorted from 3 mice.
2011-05-19 | E-GEOD-26229 | biostudies-arrayexpress
Project description:From the analysis of all genes included in the array a number of individual genes were identified as dys-regulated in HIV-1 infected patients compared to healthy controls. In particular, increased CXCL13 expression in all individual patient samples. Abstract from publication: HIV-1 infection is associated with B-cell abnormalities such as hypergammaglobulinemia, poor immunisation responses and loss of serological memory. To determine whether altered expression of chemokine receptors and their ligands may play a role in B-cell dysfunctions during HIV-1 infection, the expression of CXCR4, CXCR5 and CCR7 receptors and their respective ligands on CD19+ B-cells were examined in HIV-1 infected patients and controls. We report a decreased CXCR5 expression on B-cells from patients (p<0.05), a phenomenon associated with a low CD4 T-cell count (<350 cells/µl). Interestingly, an increased expression of CXCL13, the ligand for CXCR5, was found in peripheral B-cells from HIV-1 infected patients. Moreover upon B-cell activation in vitro, CXCL13 was secreted in culture. In addition, CXCL13 positive B-cells were also found in the lymph nodes of HIV-1 infected patients, but not in control tissue. B-cell migration towards CXCL13, CXCL12 and CCL21, ligands for CXCR5, CXCR4 and CCR7, was also evaluated. In patients with a low CD4 Tcell count, migration towards all ligands was increased. Our findings indicate that altered expression of the chemokine receptor-ligand pair, CXCR5/CXCL13 may participate in the establishment of B-cell dysfunctions during HIV-1 infection. Total RNA was extracted from purified peripheral B-cells from 4 controls and 4 patients.
2010-06-25 | E-GEOD-12597 | biostudies-arrayexpress
Project description:Chemokines and adhesion molecules upregulated in lymphatic endothelial cells (LECs) during tissue inflammation are believed to enhance dendritic cell (DC) migration to draining lymph nodes (dLNs), but the in vivo control of this process is not well understood. By performing transcriptional profiling of LECs isolated from murine skin, we found that inflammation induced by a contact hypersensitivity (CHS) response upregulated the adhesion molecules ICAM-1 and VCAM-1 and inflammatory chemokines in LECs. Furthermore, lymphatic lineage markers like Prox-1, VEGFR3 and LYVE-1 were significantly downregulated during CHS. By contrast, skin inflammation induced by Complete Freund’s adjuvant (CFA) induced a different pattern of chemokine and lymphatic marker gene expression and almost no ICAM-1 up-regulation in LECs. In FITC painting experiments, DC migration to dLNs was more strongly increased in CFA- as compared to CHS-induced inflammation. Interestingly, DC migration did not correlate with the induction of CCL21 and ICAM-1 in LECs. However, the requirement for CCR7 signaling became further pronounced during inflammation, whereas CCR7-independent signals only had a minor role in enhancing DC migration. Collectively, these findings indicate that inflammation-induced DC migration is stimulus-dependent and only moderately enhanced by LEC-induced genes other than CCL21.
2011-05-20 | GSE26229 | GEO
Project description:CCL21 is downregulated in stroma during inflammation of the lymph node. The factors controlling this repression are unknown. ATAC-seq was performed on naïve and inflamed lymph node fibroblasts to elucidate the signals controlling CCL21 downregulation and other lymph node stromal inflammatory programs.
2024-11-13 | GSE281684 | GEO
Project description:Migration and homing of immune cells are critical for immune surveillance. Efficient trafficking is mediated by cellular expression of combinations of adhesion and chemokine receptors which guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system. This supports tissue-localized immune reactions and systemic immunity. However, fundamental questions remain as to how these signals are initiated and regulated. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells from leaving the lungs and migrating to the lymph nodes. During pulmonary viral infection this dysregulation leads to plasmacytoid dendritic cells becoming retained in the lungs where they improve tissue-localized anti-viral immunity. By comparison, during chronic allergen challenge the accumulation of immune cells in the lung leads to the pronounced formation of tertiary lymphoid structures in the lung, and a failure to seed the lymph nodes. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thereby licencing the homing of CCR7+ immune cells to lymph nodes. Thus, ILC2-derived LIF production dictates the egress of immune cells from the lungs regulating tissue versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.
2024-07-30 | GSE243691 | GEO
Project description:The capacity of dendritic cells (DC) to migrate from peripheral organs to lymph nodes (LN) is an important event in the initiation of a T cell-mediated immune response. Previously it was shown that the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; ABCB1) and the 2 multidrug resistance protein 1 (MRP1; ABCC1) play a role in both human and murine DC migration. Here we show that a more recently discovered family-member, MRP4 (ABCC4) is expressed on both epidermal and dermal human skin DC and contributes to the migratory capacity of DC. Pharmacological inhibition of MRP4 activity or down-regulation through RNAi in DC resulted in reduced migration of DC from human skin explants and of in vitro generated Langerhans cells. The responsible MRP4 substrate remains to be identified as exogenous addition of MRP4’s known substrates PGE2, leukotriene B4 and D4 or cyclic nucleotides (all previously implicated in DC migration) could not restore migration. This notwithstanding, our data show that MRP4 is an important molecule, significantly contributing to human DC migration towards the draining lymph nodes, and thereby relevant for the initiation of an immune response and a possible target for immunotherapy. Keywords: cell type comparison, RNAi knockdown for MRP4
2008-07-12 | GSE12089 | GEO