Single cell transcriptome signatures and cell-cell interactions associated with sarcoidosis in lung immune cell populations

BackgroundSarcoidosis is a complex, multi-system granulomatous disease characterized by immune dysregulation and chronic inflammation, primarily affecting the lungs. To identify cell specific molecular changes associated with sarcoidosis development and progression, we aimed to characterize cellular composition, gene expression patterns, and cell-cell interactions in bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis and healthy controls.MethodsSingle cell RNA-seq on 16 sarcoidosis cases (8 progressive and 8 non-progressive) and 14 controls were analyzed to identify differences in cell proportions by disease group using F-tests and differential gene expression (DE) using pseudobulk analysis.

Enriched pathways and upstream regulators were identified using Ingenuity Pathway Analysis (IPA). Cell-to-cell communication and ligand-receptor interaction analyses were performed using CellChat.ResultsWe identified significant DE of genes and pathways associated with sarcoidosis in resident macrophages (upregulation of IL1R1, PSTPIP2, TAPBP), recruited macrophages (downregulation of AKT1, ACKR3, AZU1), and proliferating macrophages (upregulation of CCL4).

We also observed a limited number of DE transcripts associated with disease progression in resident and recruited macrophages. In non-macrophages cells, we observed a significant reduction in the number of B cells in sarcoidosis.