GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE290nnn/GSE290458/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE290458GEOGSEfalseIFN-γ induction of GBP1 drives aberrant macrophage activation in human skin granulomasGranuloma annulare (GA) and cutaneous sarcoidosis (cSAR), non-communicable skin conditions, possess an overlapping immunopathology, in which the aberrant activation of macrophages by IFN-γ constitutes a central driver of disease. Nevertheless, our understanding of the molecular events occurring in pathologically activated GA and cSAR macrophages remains limited. Here, we analyzed published single-cell RNA sequencing data of GA and cSAR and performed in-vitro experiments with primary human cells, allowing us to show that oxidative phosphorylation (OXPHOS) is a dominant metabolic pathway in IFN-γ-activated macrophages. Furthermore, we identify an IFN-γ-induced, OXPHOS-sensitive response network in human GA and cSAR macrophages. Within this network, GBP1 plays a central role in controlling IFN-γ-mediated macrophage activation. Meanwhile, inhibition of OXPHOS and GBP1 both promoted resolution of granulomas and prevented granuloma induction in a human in-vitro granuloma model. Taken together, our study suggests that OXPHOS and GBP1 represent therapeutic strategies for treating cutaneous granulomatous diseases.2026/04/18GSE290458GSM8814870GSM8814871GSM8814850GSM8814851GSM8814830GSM8814852GSM8814853GSM8814831GSM8814854GSM8814832GSM8814833GSM8814855GSM8814856GSM8814834GSM8814857GSM8814835GSM8814836GSM8814858GSM8814859GSM8814837GSM8814838GSM8814839GSM8814860GSM8814861GSM8814862GSM8814840GSM8814863GSM8814841GSM8814842GSM8814864GSM8814865GSM8814843GSM8814866GSM8814844GSM8814845GSM8814867GSM8814868GSM8814846GSM8814847GSM8814825GSM8814869GSM8814848GSM8814826GSM8814827GSM8814849GSM8814828GSM881482921290290458Homo sapiens