RESUMO
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 are 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 Food and Drug Administration-approved therapies despite the significant impact of GA on QOL. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissues, 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 6 patients with GA. Our findings revealed mixed T helper 1 and T helper 2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN-γ and TNF signals emerged as important regulators of GA granulomatous inflammation, and IL-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.
RESUMO
Inflammation is a hallmark of remitting-relapsing dermatological diseases. Although a large emphasis has been placed on adaptive immune cells as mediators of relapse, evidence in epithelial and innate immune biology suggests that disease memory is widespread. In this study, we bring to the fore the concept of inflammatory memory or nonspecific training of long-lived cells in the skin, highlighting the epigenetic and other mechanisms that propagate memory at the cellular level. We place these findings in the context of psoriasis, a prototypic flaring disease known to have localized memory, and underscore the importance of targeting memory to limit disease flares.