Increased homing of immune cells by orexigenic catecholaminergic neurons alleviates autoimmune disorder
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA717968 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14086738_1.fastq.gz | Fastqsanger.gz | |||
| SRR14086738_2.fastq.gz | Fastqsanger.gz | |||
| SRR14086739_1.fastq.gz | Fastqsanger.gz | |||
| SRR14086739_2.fastq.gz | Fastqsanger.gz | |||
| SRR14086740_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 32 |
Similar Datasets
Project description:Whole-body energy status significantly impacts the immune system. Both feeding behavior and energy metabolism are controlled by the central nerve system, but it is unknown whether the brain can regulate the immune system in response to fluctuations of the energy status. Here, we show that catecholaminergic (CA) neurons in the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM) were activated by fasting, and demonstrate that chemogenetic activation of these hindbrain CA neurons both increased food intake and drove homing of CD45+ cells, T cells, and B cells from blood to bone marrow, which was mediated by enhanced HPA axis and upregulation of the chemokine receptor CXCR4. This activation of CA neurons also prevented immune cell infiltration to the brain in the experimental autoimmune encephalomyelitis (EAE) mouse model, and ameliorated the disease outcome. Our study demonstrates the neuronal control of immune function in response to host energy scarcity and sheds light on communications between the nervous and immune systems.
2024-03-01 | GSE170737 | GEO
Project description:Metastatic cell homing is a complex process mediated in part by diffusible factors secreted from immune cells found at a pre-metastatic niche. We report on connecting together secretomics and a TRanscriptional Activity CEll aRray (TRACER) to identify functional paracrine interactions between immune cells and metastatic cells as novel mediators of metastatic cell homing. Splenocytes from orthotopic mouse models of breast cancer were isolated to generate a diseased splenocyte conditioned media (D-SCM) containing immune cell secreted factors. MDA-MB-231 metastatic cell activity including cell invasion, migration, transendothelial migration, and proliferation were increased when cultured with D-SCM compared to healthy SCM (H-SCM) and unconditioned media controls. Our secretome analysis of D-SCM yielded secreted factor candidates that contribute to increased metastatic cell activity. In parallel, we identified active TFs within metastatic cells in response to the secreted factors using TRACER. We connected both data sets using MetaCore software to determine interactions between immune cell secreted factors and active metastatic cell TFs to narrow down functional secreted factor candidates that mediate metastatic cell homing. Haptoglobin was among the list of secreted factors and was validated in vitro as a key mediator of metastatic cell recruitment. Furthermore, we designed an implantable poly(lactide-co-glycolide) biomaterial scaffold as a mimic of the pre-metastatic niche to slowly release haptoglobin and demonstrate increased homing of metastatic cells to the scaffold in vivo. Taken together, our studies demonstrate a novel systems biology technique to identify functional paracrine signaling factors, which were validated to reveal mediators of metastatic cell homing.
2015-12-17 | PXD002051 | Pride
Project description:Glioblastoma is the most common and most devastating adult primary brain tumor. Despite aggressive multimodal therapy, the median survival is approximately one year after diagnosis. In recent years bone marrow-derived human mesenchymal stem cells (BM-hMSCs) have shown promise as cell-based delivery vehicles for anti-glioma therapeutics. This is largely due to their innate ability to migrate towards gliomas. Several studies have successfully demonstrated their use as delivery vehicles for anti-glioma agents. However, it is now evident that BM-hMSCs demonstrate variable tropism towards gliomas based on a clinically relevant glioma stem cell (GSC) model of GBM. In this study, we compared the proteomic profile of cancer and stromal cell populations in GSC xenografts that attract BM-hMSCs (‘attractors’) with those to do not (‘non-attractors’) in order to identify cell-signaling pathways that may modulate BM-hMSCs homing followed by targeted transcriptomic analysis of human gene sets related to glioma biology. We identified lower protein expression of fatty acid metabolism and glucose-dependent metabolic pathways in attractors. While transcriptomic analysis suggested that N-linked glycosylation was increased. Conversely, glucose metabolic pathways, including oxidative phosphorylation, were increased in the stromal cells present in attractors. The results presented here provide the first evidence for glucose metabolism, reactive oxidative species and lipid-mediated tumor inflammatory response, and N-linked glycosylation in the homing of BM-hMSC to GSC xenografts. Reciprocal expression of these pathways in the stromal cell population may suggest microenvironment cross-talk. Our studies provide new insights on the signaling correlates underlying the differential homing capacity of BM-hMSCs to GSC xenografts.
2016-02-17 | PXD001778 | Pride
Project description:Increased IL-6 and altered inflammatory response in bipolar disorder patient-derived astrocytes
| PRJNA661540 | ENA
Project description:Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer. This SuperSeries is composed of the following subset Series: GSE15748: Gene expression in PLN vs. ILN or MLN in mice GSE15753: Gene expression in GLN versus PDLN in NOD mice Refer to individual Series
2009-04-23 | E-GEOD-15784 | biostudies-arrayexpress
Project description:The Kruppel-like factor 5 (Klf5) regulates pluripotent stem cell self-renewal but its role in somatic stem cells is unknown. Klf5 deficient hematopoietic stem cells and progenitors (HSC/P) fail to engraft after transplantation. This HSC/P defect was associated with impaired bone marrow (BM) homing and lodging and decreased retention in BM. The Klf5Δ/Δ HSC/P homing defect associated with decreased adhesion to fibronectin and expression of membrane-bound β1/β2-integrins. In vivo inducible gain-of-function of Klf5 in HSC translated into increased HSC/P adhesion. The expression of Rab5 family members, mediators of β1/β2-integrin recycling in the early endosome, was decreased in Klf5Δ/Δ HSC/P. Klf5 binds directly to the promoter of Rab5a/b and overexpression of Rab5b rescued the expression of activated β1/β2-integrins, adhesion and BM homing of Klf5Δ/Δ HSC/P. Altogether, these data indicate that Klf5 is indispensable for adhesion, homing, lodging and retention of HSC/P in the BM through Rab5-dependent post-translational regulation of Beta1/Beta2 integrins. Differential gene expression analyses was performed with Affymetrix GeneChip Mouse 1.0 ST assay. LSK cells from KLF-/- (n=4) and wt (n=5), bred on a C57BL/6 background, was analyzed for differential gene expression using GeneSpring GX11 using student's T-test.
2013-01-30 | E-GEOD-43806 | biostudies-arrayexpress
Project description:Cavβ3 contributes to the maintenance of the blood-brain barrier and alleviates symptoms of experimental autoimmune encephalitis
| PRJNA1118801 | ENA
Project description:A candidate causal variant underlying both enhanced cognitive performance and increased risk of bipolar disorder
| PRJNA483474 | ENA
Project description:Patterns of chemotactic receptors regulate the homing of leukocytes to tissues. Here we report that the CCRL2/chemerin/CMKLR1 axis represent a selective pathway for the homing of NK cells to the lung. CCRL2 is a non-signaling seven-transmembrane domain receptor able to control lung tumor growth. Total or endothelial cell targeted CCRL2 deletion or the deletion of its ligand chemerin were found to promote tumor progression in a KrasG12D/+;p53LoxP lung cancer model. This phenotype was dependent on the reduced recruitment of CD27-CD11b+ mature NK cells. Mining scRNA-seq databases identified CCRL2 expression as the hallmark of general alveolar lung capillary endothelial cells (gCaps). CCRL2 expression is epigenetically regulated in lung endothelium. In vivo administration of low doses of the demethylating agent 5-Aza induced CCRL2 upregulation, increased recruitment of NK cells and lung protection in a tumor model. These results identify CCRL2 as a NK cell lung homing molecule that might be exploited to promote NK cell-mediated lung immune surveillance.
2023-08-04 | GSE212088 | GEO
Project description:Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer. This SuperSeries is composed of the SubSeries listed below.
2009-04-23 | GSE15784 | GEO