Follicular helper-like T cells in the lung highlight a novel role of B cells in sarcoidosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE162712 | GEO | 2021/09/07
REPOSITORIES: GEO
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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:Sarcoidosis is characterized by exaggerated immune response to unknown agent and can affect different organs. One of the main players in the pathology of the disease are regulatory T cells (Tregs), however up to date there are no insides on the possible molecular alterations of this particular cell subset. Therefore, in the current study we looked for the global changes on miRNA and mRNA level of Tregs of patients with the most predominant form of the disease - pulmonary sarcoidosis (PS). For this purpose we sorted Treg cells from peripheral blood (PB) and bronchoalveolar lavage (BAL) and analyzed the global molecular changes. MiRNA analysis showed major changes in Tregs isolated from PB to the ones from BAL, pointing at the stronger impact of the microenvironment than the disease state. Additionally, several disease-related miRNAs of PB Tregs were identified like miR-155 and miR-223.
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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:Sarcoidosis is a disease that affects multiple organ systems, with lung disease seen commonly and is the most frequent cause of sarcoidosis-related mortality. We investigated to compare protein expression in the lung from both bronchoalveolar lavage fluid (BAL) cells and fluid (BALF) in newly diagnosed patients with sarcoidosis. Mass spectral data acquisition was conducted on an Orbitrap Fusion instrument in data-dependent mode using either label-free (BALF) or label-based (intracellular) approach. We identified 4,306 high confidence intracellular proteins (probability >99%) with 272 differentially expressed proteins controlling for an FDR 5%. The protein map to several known canonical pathways including phagosome maturation, clathrin-mediated endocytic signaling, NRF-2 mediated oxidant stress response, The examination of BALF identified 1,192 proteins, xxx and xxx protein with differential expression between controls vs. sarcoidosis and progressive vs. non-progressive sarcoidosis respectively. Several of the proteins identified mapping to the differentially expressed proteins were also detected in the BALF.
2021-09-08 | PXD014438 | Pride
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:Investigate the differences between Sarcoidosis and Controls as well as between progressive and nonprogressive pulmonary sarcoidosis using 2D LC-MS/MS proteomics instrumentation and bronchoalveolar lavage samples. MaxQuant was used for database searches label free quantitation followed by Ingenuity Pathway Analysis to identify pathways of differentially expressed proteins and potential biomarkers.
2021-09-09 | PXD016637 | Pride
Project description:We profiled DNA methylation, mRNA expression, and miRNA expression from bronchoalveolar lavage cells obtained from 64 sarcoidosis subjects and 16 healthy controls.
2024-08-08 | GSE263448 | GEO
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:We profiled DNA methylation, mRNA expression, and miRNA expression from bronchoalveolar lavage cells obtained from 64 sarcoidosis subjects and 16 healthy controls.
2024-08-08 | GSE263451 | GEO