American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2024
Single-Cell Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.
Rationale: Fibrotic hypersensitivity pneumonitis (FHP) is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in FHP in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and BAL cells obtained from 45 patients with FHP, 63 patients with idiopathic pulmonary fibrosis (IPF), 4 patients with nonfibrotic hypersensitivity pneumonitis, and 36 healthy control subjects in the United States and Mexico. ⋯ These results are publicly available at http://ildimmunecellatlas.com. Conclusions: Single-cell transcriptomics of patients with FHP 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 IPF. Both cell populations may guide the development of new biomarkers and therapeutic interventions.
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Am. J. Respir. Crit. Care Med. · Nov 2024
Lung Tissue Multi-Layer Network Analysis Uncovers the Molecular Heterogeneity of COPD.
Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics. Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. ⋯ Finally, using spatial transcriptomics, we characterized the small airway differences between C#3 and C#4, identifying an upregulation of T-/B-cell homing chemokines and bacterial response genes in C#3. Conclusions: A novel multilayer network analysis is able to identify clinically relevant COPD patient communities. Patients with similarly low FEV1 and emphysema can have molecularly distinct small airways and immune response patterns, indicating that different endotypes can lead to similar clinical presentation.