Pluto Bioinformatics

GSE132338: Characterization of the immunologic impact of sarcoidosis in peripheral blood mononuclear cells via single-cell RNA-seq

Bulk RNA sequencing

Sarcoidosis is a systemic inflammatory disease characterized by infiltration of immune cells into granulomas. Previous gene expression studies using heterogeneous cell mixtures lack insight into cell-type-specific immune dysregulation. We sought to characterize cell-specific dysregulated pathways in sarcoidosis via cutting-edge technology of single-cell RNA sequencing. We performed the first single-cell RNA-sequencing study of sarcoidosis in peripheral immune cells in 48 patients and controls. Following unbiased clustering, differentially expressed genes were identified and bioinformatically assessed for function and pathway enrichment. Our results reveal persistent T cell receptor-mediated activation of effector T cells and innate activation of circulating monocytes with subsequent upregulation of trafficking molecules. Specifically, effector T cells show T cell receptor mediated activation as well as enrichment of associated metabolic pathways and regulatory pathways involving PD-1, NF"?" B, and multiple cytokines. Regulatory T cells demonstrated enrichment of PD-1 and cell death signaling and differential expression of functional genes. Classical and non-classical monocytes upregulated distinct markers of activation including adhesion molecules, pattern recognition receptors, and chemokine receptors. Classical monocytes demonstrated enrichment of immunoregulatory pathways PPAR and HOTAIR, while IL-5 and p-selectin were enriched in non-classical monocytes. Using more sensitive technology and more precise units of measure, we identify cell-type specific, novel immune and metabolic pathways characterizing sarcoidosis. We show antigen-driven Th1 T cell response, dysfunctional regulatory T cells, and innate activation and trafficking of circulating monocytes. We further our understanding of the immunopathology of sarcoidosis and point to novel diagnostic markers and potential therapeutic targets. SOURCE: Courtney,G,MontgomeryMontgomery Lab Oklahoma Medical Research Foundation