Mucosal Immunol. 2026 Jan 9:S1933-0219(26)00003-6. doi: 10.1016/j.mucimm.2026.01.003. Online ahead of print.

ABSTRACT

Silicosis is an inflammation-driven pulmonary fibrosis caused by occupational inhalation of silica particles. Macrophages are crucial in silicosis pathology, yet their interaction with stromal cells in orchestrating fibrosis progression remains poorly understood. Single-cell RNA sequencing (scRNAseq) of whole-lung lavages from silicosis patients identified the expansion of an intermediate CCL2-hi monocyte-like macrophage (MLM) cluster that further differentiated into inflammatory IL1B-hi and pre-fibrotic SPP1-hi (osteopontin) subsets. SPP1-hi MLMs showed enrichment for tissue remodelling (SPP1, CHI3L1, MMP14, COL6A1), oxidative stress (GCLC, TXN, PRDX1), and bio-mineralisation genes (GLA, CA2, CTSK). To explore immune-stromal dynamics, we developed a site-specific silicosis mouse model via mini-bronchoscopy. Mouse scRNAseq analysis and cell-cell communication modelling identified novel neutrophil subsets, reprogrammed alveolar type 2 epithelial cells, and two Sfrp1-hi/Spp1-hi fibroblast subsets involved in extensive crosstalk with MLMs. These data identify key components of the silicotic niche and predict targetable interactions within the immune-stromal axis for ameliorating disease.

PMID:41520918 | DOI:10.1016/j.mucimm.2026.01.003