RNA-Sequencing of Chronic hypersensitivity pneumonitis compared with Idiopathic Pulmonary Fibrosis and Control Lung
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ABSTRACT:
PROVIDER: PRJNA634074 | ENA |
REPOSITORIES: ENA
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Project description:Chronic hypersensitivity pneumonitis (CHP) is caused by an immune response to antigen inhalation and is characterized by variable histopathological and clinical features. A subset of CHP subjects have usual interstitial pneumonia and appear to be clinically similar to subjects with idiopathic pulmonary fibrosis (IPF). However, the molecular relationship between CHP and IPF is not well understood. We report an RNA-seq based transcriptomic analysis for whole lung tissues from CHP, IPF and control subjects.
2020-07-01 | GSE150910 | GEO
Project description:Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5’ RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFb and TNFa/NFkB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells – reflecting this disease’s unique inflammatory T-cell driven nature – as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.
2024-07-09 | GSE271789 | GEO
Project description:IL-2 inducible tyrosine kinase (Itk) is a Tec family non-receptor tyrosine kinase that is known to regulate T-helper cell differentiation and function. It has been established that Itk postively regulates T helper 17 cells. However, in a model of hypersensitivity pneumonitis we found T helper 17 cells develop independently of Itk. Therefore, we compared the transcriptomes of WT and Itk-/- T helper 17 cells following exposure with Saccharopolyspora rectivirgula by RNA sequencing.
2024-01-28 | GSE165711 | GEO
Project description:Lung microenvironments and disease progression in fibrotic hypersensitivity pneumonitis
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Project description:Idiopathic pulmonary fibrosis (IPF)
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Project description:Despite recent improvements in management of idiopathic pulmonary arterial hypertension, mortality remains high. Understanding the alterations in the transcriptome–phenotype of the key lung cells involved could provide insight into the drivers of pathogenesis. In this study, we examined differential gene expression of cell types implicated in idiopathic pulmonary arterial hypertension from lung explants of patients with idiopathic pulmonary arterial hypertension compared to control lungs. After tissue digestion, we analyzed all cells from three idiopathic pulmonary arterial hypertension and six control lungs using droplet-based single cell RNA-sequencing. After dimensional reduction by t-stochastic neighbor embedding, we compared the transcriptomes of endothelial cells, pericyte/smooth muscle cells, fibroblasts, and macrophage clusters, examining differential gene expression and pathways implicated by analysis of Gene Ontology Enrichment. We found that endothelial cells and pericyte/smooth muscle cells had the most differentially expressed gene profile compared to other cell types. Top differentially upregulated genes in endothelial cells included novel genes: ROBO4, APCDD1, NDST1, MMRN2, NOTCH4, and DOCK6, as well as previously reported genes: ENG, ORAI2, TFDP1, KDR, AMOTL2, PDGFB, FGFR1, EDN1, and NOTCH1. Several transcription factors were also found to be upregulated in idiopathic pulmonary arterial hypertension endothelial cells including SOX18, STRA13, LYL1, and ELK, which have known roles in regulating endothelial cell phenotype. In particular, SOX18 was implicated through bioinformatics analyses in regulating the idiopathic pulmonary arterial hypertension endothelial cell transcriptome. Furthermore, idiopathic pulmonary arterial hypertension endothelial cells upregulated expression of FAM60A and HDAC7, potentially affecting epigenetic changes in idiopathic pulmonary arterial hypertension endothelial cells. Pericyte/smooth muscle cells expressed genes implicated in regulation of cellular apoptosis and extracellular matrix organization, and several ligands for genes showing increased expression in endothelial cells. In conclusion, our study represents the first detailed look at the transcriptomic landscape across idiopathic pulmonary arterial hypertension lung cells and provides robust insight into alterations that occur in vivo in idiopathic pulmonary arterial hypertension lungs.
2021-03-24 | GSE169471 | GEO
Project description:Serum EV proteome of Idiopathic Pulmonary Fibrosis patients using DIA analysis
2025-03-04 | PXD042707 | JPOST Repository
Project description:RNAseq in Idiopathic Pulmonary Fibrosis
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Project description:Single-Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis
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Project description:Approximately 60-70% of patients with pulmonary sarcoidosis have a good outcome, with disease that resolves spontaneously. It is unclear why some patients progress to fibrotic disease, and there is currently no marker that differentiates these patients from those with self-limiting lung disease. Using the Affymetrix Human Gene 1.0 ST Array, we examined gene expression in lung tissue samples obtained using bronchoscopic transbronchial biopsy from 8 patients with active but self-limiting pulmonary sarcoidosis and 7 with active, progressive, fibrotic pulmonary disease. Analyses were performed to identify differentially expressed genes between the two groups, and to test for enrichment of sets of genes associated with defined biological processes from the Gene Ontology Consortium, as well as with gene sets derived from published data for idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP).
2010-01-31 | GSE19976 | GEO