Granulomas and disease in sarcoidosis

Aggregation of hypertrophic macrophages constitutes the basis of granulomatous diseases such as sarcoidosis and is decisive for disease pathogenesis. However, macrophage-inherent pathways driving granuloma initiation and their role for T-cell activation remain poorly understood. We have recently shown that chronic activation of the metabolic checkpoint kinase mTORC1 in macrophages is sufficient to induce granuloma formation in mice and is associated with disease progression in sarcoidosis patients. The central aim of this research application is the elucidation of whether a dysregulation of a metabolic and inflammatory circle intrinsically in macrophages and driven by mTORC1 can initiate granuloma formation and drives T-cell dysfunction in sarcoidosis. The elucidation of novel processes that drive granuloma initiation and T-cell activation will have important implications for our understanding of granulomatous diseases. Assessing the metabolic and inflammatory role of the mTORC1 pathway for granulomas in macrophages may provide novel therapeutic strategies to granulomatous diseases such as sarcoidosis.