336 Induced pluripotent stem cell-derived macrophages in an inflammatory skin disease model to study granuloma formation

Granulomas are aggregates of immune cells that can form in various organs. In cutaneous sarcoidosis macrophages and T present inside granuloma cores not able to eliminate the yet unknown antigen arrest an state causing tissue destruction. We aim study switch a protective cell phenotype pathological, disease-driving population within granulomas. Therefore, we use combination direct visualization, RNA sequencing analysis isolated sophisticated co-culture models, including induced pluripotent stem cell-derived (iPSM) together with patient-derived fibroblasts. The differentiation iPSM was successfully established surface marker expression compared monocyte-derived (MoMac) from same individuals. detected comparable levels canonical macrophage markers CD14 CD68, subtype specific CD80 (M1) CD206 (M2) secretion TNFα IL-4. To identify potential pathways MoMac relevant granuloma-associated macrophages, performed bulk single-cell iPSM, skin lesions. Interestingly, found enriched interferon response, TNF signaling via NFκB metabolic (oxidative phosphorylation glycolysis) skin-derived patients healthy controls. incorporated into equivalents showed trend towards aggregation control cells, which were evenly distributed extracellular matrix. will now determine role these pathological more detail.