Single-cell transcriptomics of bronchoalveolar lavage reveals divergent macrophage subpopulations and trajectories in interstitial lung disease

RESULTS: We identified sixteen distinct cell populations in BAL with notable differences across ILD subtypes. Analysis revealed six monocyte-like macrophage (MLM) subclusters following divergent trajectories: inflammatory CXCL10hi MLMs predominated in hypersensitivity pneumonitis, while pro-fibrotic SPP1hi MLMs were significantly expanded in IPF. Short-telomere patients demonstrated an increased proportion of pro-fibrotic SPP1hi MLMs with enhanced expression of fibrotic genes compared to patients with normal telomere length.

Integration with genomic data confirmed that SPP1hi and CCL2hi MLM subclusters harbour cells with the highest IPF disease relevance scores. CONCLUSION: BAL-derived transcriptomics reveals distinct myeloid subpopulations across ILD subtypes, with specific populations associated with disease pathogenesis. These findings provide insight into ILD pathogenesis, motivate the development of more sophisticated diagnostic tests using BAL sampling, and highlight specific myeloid subpopulations as potential therapeutic targets.