Transcriptional characterization of mononuclear phagocytes (MNP) in blood and BAL of healthy and sarcoidosis patients
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PROVIDER: PRJNA730909 | ENA |
REPOSITORIES: ENA
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Project description:Pulmonary sarcoidosis is an inflammatory disease characterized by granuloma formation and heterogeneous clinical outcome. TNF is a proinflammatory cytokine contributing to granuloma formation and high levels of TNF have been shown to associate with progressive disease. Mononuclear phagocytes (MNPs) are potent producers of TNF and highly responsive to inflammation. In sarcoidosis, alveolar macrophages (AMs) have been well studied. However, MNPs also include monocytes/monocyte-derived cells and dendritic cells (DCs) that despite their central role in inflammation are poorly studied in sarcoidosis. We performed in-depth phenotypic, functional and transcriptomic analysis of MNPs subsets from blood and bronchoalveolar lavage (BAL) fluid from 108 sarcoidosis patients and 30 healthy controls.
2021-05-19 | GSE174659 | GEO
Project description:The small intestine contains lymph node-like structures termed Peyer’s patches (PP). In adult mice they contain active germinal centers reminiscent of active crosstalk with microbiota. In neonatal mice, however, homeostatic immune activation does not take place. We wanted to test whether immune maturation in neonatal mice is stalled due to a reduced presence or function of antigen presenting mononuclear phagocytes (MNP). Thus we subjected PP MNP of postnatal day (PND) 11 and adult mice to scRNAseq in steady state or after immune activation with the TLR7 agonist R848 that induces type I interferon and TNFa after oral gavage. Our results show an altered subset distribution of MNP in neonatal mice (predominance of cDC1 and cDC2b, reduced proportion of cDC2a) and a reduced potential to take up microorganisms and process/present antigen as well as decreased type I interferon mediated gene expresseion. R848 administration could partly overcome this maturation defect of neonatal MNP by increasing the proportion of CCR7+ mature cDC as well as upregulation of interferon I dependent genes.
2022-12-31 | GSE188714 | GEO
Project description:Whole genome mRNA and microRNA profiling of bronchoalveolar lavage (BAL) and peripheral blood mononuclear cell (PBMC) in Sarcoidosis patients
2020-12-08 | GSE109516 | GEO
Project description:scRNAseq of cecum mononuclear phagocytes of PBS/LPS-treated mice
| PRJEB46461 | ENA
Project description:Primary RNASeq data for progenitor, resident, and stimulated (C.alb, LPS, injury, APAP+ starved overnight and pIC) mononuclear phagocytes from fourteen organs.
2018-11-03 | GSE122108 | GEO
Project description:ImmGen ULI: OpenSource Mononuclear Phagocytes Project
| PRJNA503607 | ENA
Project description:Introduction: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in alveolar macrophagesâa key immuno-inflammatory cell in the lungâcan shed light on the pathogenesis of this complex disease. Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from bronchoalveolar (BAL) cells and hybridized to an Affymetrix GeneChip Human Genome U133A 2.0 microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we applied gene set enrichment analysis (GSEA) to the transcriptional profiles of BAL cells. We used false discovery rate (FDR) < 0.01 to designate significant enrichment. Results: Sarcoid patients were either non-smokers or ex-smokers, all had lung involvement and only 2 were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1200 differentially expressed genes at an FDR cutoff < 0.01. Several previously described immune mediators, such as interferon gamma, were up-regulated in the sarcoidosis subjects. Since genes often exert their influence through functionally coherent modules, we performed GSEA based on global expression profiles of alveolar macrophages between the subject groups. We identified more than 200 gene sets enriched in patients with sarcoidosis whereas very few pathways were over-represented in the healthy controls. Many of the sarcoidosis-associated pathways mapped to inflammatory and immune-related processes including T-cell signaling, graft vs. host disease, IL-12, IL-23, and IL-17 pathways, and oxidative phosphorylation. However, we also found and confirmed significant alteration in Proteasome-related pathways. Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional networks involved in immuno-inflammatory and proteasomal processes. Our findings add to the growing evidence implicating airspace resident cells in the pathogenesis of sarcoidoisis and identify specific pathways whose activation may modulate disease progression. Total RNA from BAL cells of 15 subjects with sarcoidosis and 12 healthy controls was hybridized to 27 Affymetrix Genechip Human U133A 2.0 microarrays
2016-07-22 | E-GEOD-75023 | biostudies-arrayexpress
Project description:Introduction: Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in alveolar macrophages—a key immuno-inflammatory cell in the lung—can shed light on the pathogenesis of this complex disease. Methods: We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from bronchoalveolar (BAL) cells and hybridized to an Affymetrix GeneChip Human Genome U133A 2.0 microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we applied gene set enrichment analysis (GSEA) to the transcriptional profiles of BAL cells. We used false discovery rate (FDR) < 0.01 to designate significant enrichment. Results: Sarcoid patients were either non-smokers or ex-smokers, all had lung involvement and only 2 were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1200 differentially expressed genes at an FDR cutoff < 0.01. Several previously described immune mediators, such as interferon gamma, were up-regulated in the sarcoidosis subjects. Since genes often exert their influence through functionally coherent modules, we performed GSEA based on global expression profiles of alveolar macrophages between the subject groups. We identified more than 200 gene sets enriched in patients with sarcoidosis whereas very few pathways were over-represented in the healthy controls. Many of the sarcoidosis-associated pathways mapped to inflammatory and immune-related processes including T-cell signaling, graft vs. host disease, IL-12, IL-23, and IL-17 pathways, and oxidative phosphorylation. However, we also found and confirmed significant alteration in Proteasome-related pathways. Conclusions: BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional networks involved in immuno-inflammatory and proteasomal processes. Our findings add to the growing evidence implicating airspace resident cells in the pathogenesis of sarcoidoisis and identify specific pathways whose activation may modulate disease progression.
2016-07-22 | GSE75023 | GEO
Project description:The mononuclear phagocytic system (MPS) is characterized by functional diversity and plasticity, including within the tumor microenvironment (TME). Tumor-associated mononuclear phagocytes (TMPs) within the TME come from various ontological origins. To determine how Fcmr deficiency might impact the functional heterogeneity of mature mononuclear phagocytes (MPs) within the TME, we performed single-cell RNA sequencing (scRNAseq) on MPs isolated from B16 tumors resected from Fcmr-/- and Fcmr+/+ mice. To evaluate a homogenous population of MPs within the TME we chose to examine cells harboring expression of markers found in more mature, differentiated MPs. Therefore, we then sorted MerTk+ CD64+ TMPs by FACS and subjected these cells to single-cell transcriptomic analyses using the Chromium 10X Genomics platform. We obtained RNAseq profiles from 6352 Fcmr+/+ and 7999 Fcmr-/- TMPs.
2019-06-18 | GSE130287 | GEO
Project description:Background: We got interested whether genes of airway basal cells are enriched in sarcoidosis. Methods: Bronchoscopy with bronchoalveolar lavage (BAL) was performed in 26 patients with sarcoidosis, chest-x-ray type III and IV, and 20 healthy donors and isolated BAL cells.Transcriptome of BAL cells were studied by using Affymetrix Human Affymetrix Whole-Transcript Human Gene 1.0 ST array on an Affymetrix platform. Microarray data were imported, log2-transformed and quantile normalized using robust multi-array average (RMA). We tested enrichment for airway basal cells by global enrichment analysis. Results: we did not find enrichment of airway basal cell genes in sarcoidosis compared to healthy volunteers.
2018-12-31 | GSE73394 | GEO