scRNA-seq based gene and cell dynamics behind the formation of the non-caseating granulomas

Granulomas are organized aggregates of immune cells that develop during chronic inflammation when the body attempts to isolate persistent foreign substances. They can result from infections, autoimmune disorders, or exposure to foreign materials, often leading to organ dysfunction such as chronic pulmonary inflammation and diagnostic challenges. Although granulomas are well-documented histologically, their molecular mechanisms remain poorly understood. This study employed single-cell RNA sequencing (scRNA-seq) data analysis to elucidate the genetic and immunological basis of non-caseating granuloma formation, using sarcoidosis and tattoo uveitis as representative models. scRNA-seq data from healthy controls and patients with active sarcoidosis and both active and inactive tattoo uveitis were retrieved from the Sequence Read Archive (SRA), preprocessed, and analyzed using R-based computational tools. Key analyses included differential gene expression, functional enrichment, pseudotime trajectory mapping of cell dynamics, and intercellular communication network analysis. The study identified 506 granuloma-associated genes, delineated their cellular involvement, and highlighted ten immune signaling pathways potentially driving granuloma formation. These findings provide molecular insights into the pathogenesis of non-caseating granulomas and may inform future diagnostic and therapeutic strategies. However, as the analyses are based on scRNA-seq-driven in-silico interrogation, validation in larger, well-characterized cohorts and through independent experimental approaches will be essential to establish the robustness and translational potential of the reported findings.