1006 Single-cell and spatial architecture of human tissue granulomas reveals an aberrant immune-regulatory program underlying sarcoidosis

Granulomatous disorders include a wide variety of infectious and non-infectious conditions with heterogeneous clinical courses considerable constraints affected organs. We take cutaneous sarcoidosis as model disease to acquire new insights into the pathomechanisms granulomas. combined single-cell high-dimensional spatial transcriptomics fluorescently labeled antibody detection for protein expression in granulomatous non-affected skin from 12 patients chronic sarcoidosis. To identify intrinsic dysregulations immune cells we performed functional vitro assay comparing monocyte-derived macrophages healthy controls. found Th17.1 activating macrophages, fibroblasts endothelial by producing GM-CSF interferon-gamma. Macrophages attract retain structural within granuloma structures secreting chemokines remodeling extra cellular matrix. Granuloma-associated are characterized active metabolic pathways, particular mTOR, oxidative phosphorylation cholesterol metabolism. Using confirmed spontaneous clustering that was associated an activation pathways. displayed non-immune landscape granuloma. As granuloma-associated display aberrant lipid metabolism, inferring metabolism could represent additive treatment option disorders.