Granuloma annulare exhibits mixed immune and macrophage polarization profiles with spatial transcriptomics

Granuloma annulare (GA) is an idiopathic condition characterized by granulomatous inflammation in the skin. Prior studies have suggested that GA develops from various triggers, leading to a complex interplay involving innate and adaptive immunity, tissue remodeling, and fibrosis. Macrophages are the major immune cells comprising GA granulomas, however, the molecular drivers and inflammatory signaling cascade behind macrophage activation is poorly understood. Histologically, GA exhibits both palisaded and interstitial patterns on histology, however the molecular composition of GA at the spatial level remains unexplored. GA is a condition without FDA-approved therapies despite the significant impact of GA on quality of life. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissue with emerging applications in clinical medicine. To improve our understanding of the spatially localized gene expression patterns underlying GA, we profiled the spatial gene expression landscape from six patients with GA. Our findings revealed mixed Th1 and Th2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN- and TNF signals emerged as important regulators of GA granulomatous inflammation and interleukin-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.