An international research team, with major contributions from scientists at the DZL site BREATH, has for the first time investigated in detail how cells interact within chronic sarcoidosis granulomas in the lung. The results show that different cell types are closely connected, collectively influencing the formation, persistence, and progression of the disease.
Sarcoidosis is an inflammatory disease of unknown cause, primarily affecting the lungs. In some patients, it progresses to fibrosis, a gradual scarring of lung tissue. A hallmark of the disease is the formation of granulomas – distinctive clusters of immune cells, B and T lymphocytes, and fibroblasts. Until now, it was unclear which cellular programs and interactions drive this dysregulation.
The researchers used an innovative method that combines gene activity with the spatial location of cells (spatial transcriptomics). This approach allowed them to analyze over 30,000 data points from lung samples and map gene expression patterns within granulomas and their surroundings. The technique enables the study of individual cellular niches directly in their natural tissue context.
At the center of the granulomas are macrophages that simultaneously activate both inflammatory and fibrotic programs. This “hybrid” cell identity had not been described before and demonstrates that the classical separation of inflammation and fibrosis is often too simplistic.
Surrounding these central macrophages are T and B cells, while fibrotic niches are characterized by increased expression of collagen and matrix-remodeling genes. Analyses of cell communication indicate active interactions between different cell types, suggesting that inflammation and tissue remodeling are closely linked and jointly contribute to disease chronicity.
These findings are particularly relevant for translational lung research: they show that inflammation and fibrosis should not be viewed as separate processes but as a functional unit of interconnected cell networks.
The results provide a mechanistic basis for new therapeutic approaches aimed specifically at the disease-driving cellular structures in the lung.
“Our data show that granulomatous inflammation and fibrosis cannot be understood as separate processes. To develop targeted therapies in the future, we must address these locally organized cellular networks as a functional unit – not individual cell types in isolation,” emphasize the first authors and BREATH early-career researchers Leonard Christian and Hande Yilmaz.
Original publication: Leonard C, Hande Y, Jannik R et al. Spatial Transcriptomics Uncovers Hybrid, Pro-Inflammatory and Pro-Fibrotic Cellular Niches in Pulmonary Granuloma of Patients with Chronic Sarcoidosis, American Journal of Respiratory and Critical Care Medicine, 2026; aamaf089
Source: BREATH
