Project description:The goal of this study was to determine the effect of dexamethasone treatment on trancriptional sigantures and pathways of sarcoidosis monocytes.
Project description:The goal of this study was to determine the effect of dexamethasone treatment on trancriptional signatures and pathways of sarcoidosis AMs.
2020-05-20 | GSE150842 | GEO
Project description:Trancriptional signatures of dexamethasone-treated sarcoidosis alveolar macrophages (AMs)
Project description:Sarcoidosis is a multisystemic disease characterized by non-caseating granuloma infiltrating various organs. The form with symptomatic muscular involvement is called muscular sarcoidosis. The impact of immune cells composing the granuloma on the skeletal muscle is misunderstood. Here, we investigated the granuloma-skeletal muscle interactions through spatial transcriptomics. Five major transcriptomic clusters corresponding to perigranuloma, granuloma, and three successive muscle tissue areas (proximal, intermediate and distal) around the granuloma were identified. Analyses revealed upregulated pathways in the granuloma corresponding to the activation of T-lymphocytes and monocytes/macrophages cytokines and upregulation of extracellular matrix signatures and induction of the TGF-β signaling in the perigranuloma. Comparison between proximal and distal muscles to the granuloma revealed an inverse correlation between distance to the granuloma and upregulation of cellular response to interferon-γ/α, TNF-α, IL-1,4,6, fibroblast proliferation, epithelial to mesenchymal cell transition and downregulation of muscle gene expression. These data shed light on the intercommunications between granulomas and the muscle tissue and provides pathophysiological mechanisms by showing that granuloma immune-cells have a direct impact on proximal muscle tissue by promoting its progressive replacement by fibrosis via the expression of pro-inflammatory and pro-fibrosing signatures. These data could possibly explain the evolution towards a state of disability for some patients.
Project description:Cardiac involvement is an important determinant of mortality amongst sarcoidosis patients. While granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain unresolved. Furthermore, it is unclear how the cellular and transcriptomic landscape of cardiac sarcoidosis differs from other inflammatory heart diseases. We leveraged spatial transcriptomics (GeoMx DSP) and single nucleus RNA sequencing (snRNAseq) to elucidate the cellular and transcriptional landscape of cardiac sarcoidosis. Using GeoMX DSP technology, we compared the transcriptomal profile of CD68+ rich immune cell infiltrates in human cardiac sarcoidosis, giant cell myocarditis, and lymphocytic myocarditis. We performed snRNAseq of human cardiac sarcoidosis to identify immune cell types and examined their transcriptomic landscape and regulation. Using multi-channel immunofluorescence staining, we validated immune cell populations identified by snRNAseq, determined their spatial relationship, and devised an immunostaining approach to distinguish cardiac sarcoidosis from other inflammatory heart diseases. Despite overlapping histological features, spatial transcriptomics identified transcriptional signatures and associated pathways that robustly differentiated cardiac sarcoidosis from giant cell myocarditis and lymphocytic myocarditis. snRNAseq revealed the presence of diverse populations of myeloid cells in cardiac sarcoidosis with distinct molecular features. We identified GPNMB as a novel marker of multinucleated giant cells and predicted that the MITF family of transcription factors regulated this cell type. We also detected additional macrophage populations in cardiac sarcoidosis including HLA-DR+ macrophages, SYTL3+ macrophages and CD163+ resident macrophages. HLA-DR+ macrophages were found immediately adjacent to GPMMB+ giant cells, a distinct feature compared with other inflammatory cardiac diseases. SYTL3+ macrophages were located scattered throughout the granuloma and CD163+ macrophages, CD1c+ dendritic cells, non-classical monocytes, and T-cells were located at the periphery and outside of the granuloma. Finally, we demonstrate mTOR pathway activation is associated with proliferation and is selectively found in HLA-DR+ and SYLT3+ macrophages. In this study, we identified diverse populations of immune cells with distinct molecular signatures that comprise the sarcoid granuloma. These findings provide new insights into the pathology of cardiac sarcoidosis and highlight opportunities to improve diagnostic testing.
Project description:This study used whole blood transcriptional signatures from patients with sarcoidosis before and during immunosuppressive treatment
Project description:Whole blood and purified leucocyte populations were compared to determine which cell types the whole blood interferon-inducible signature, found in both tuberculosis and sarcoidosis, was present in. This study agreed with previous publication that the neutrophil was the dominant cell in tuberculosis and also showed it was the dominant cell type in sarcoidosis. There were 5 patients in each group of healthy controls, tuberculosis and sarcoidosis. The cell types were whole blood, PBMCs, monocytes (CD14), T cells (CD8 and CD4) and neutrophils (CD15).
Project description:This study used whole blood transcriptional signatures from patients with tuberculosis compared to those with similar pulmonary diseases, sarcoidosis, pneumonia and primary lung cancer. TB and sarcoidosis had similar signatures that were distinct from pneumonia and lung cancer. There were 16 TB, 25 sarcoidosis, 8 pneumonia, 8 lung cancer and 38 healthy controls
Project description:This study used whole blood transcriptional signatures from patients with tuberculosis compared to those with similar pulmonary diseases, sarcoidosis, pneumonia and primary lung cancer. TB and sarcoidosis had similar signatures that were distinct from pneumonia and lung cancer. There were 11 TB, 25 sarcoidosis, 6 pneumonia, 8 lung cancer and 52 healthy controls
Project description:This study used whole blood transcriptional signatures from patients with sarcoidosis before and during immunosuppressive treatment There were 7 pneumonia patients, the same patients were sampled before and after their treatment