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

ESDR336 - Induced pluripotent stem cell-derived macrophages in an inflammatory skin disease model to study granuloma formation

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.