Elucidating the relationship between metabolism and pathogenicity of Th17 cells 3438

Description Th17 cells are central to the pathogenesis of autoimmune disorders- like psoriasis and IBD, as well as metabolic diseases like type 2 diabetes. Inflammatory Th17 cells have been metabolically modulated in murine models to reduce disease pathogenesis, but human studies face challenges due to low Th17 abundance and in vitro models. We overcame this obstacle and established the relationship between defects in fatty acid metabolism and in vivo differentiated Th17 effector function with a novel Th17 cell enrichment assay. We captured CD4+ T cells with a hydrogel particle and magnetically purified them based on secretion of IL-17A/17F/21, allowing for us to perform scRNAseq on in vivo differentiated, activated Th17 cells. We then utilized an algorithm named scFEA- powered by scRNAseq data and flux balance analysis, to characterize the cellular metabolic state of our captured Th17 cells. Overlaying scRNAseq data from in vitro and in vivo differentiated samples with gene ontology resources and applying in-silico modeling of metabolic pathways, we identified key lipid pathways driving Th17 inflammation and conducted the first study ever to be done on in vivo differentiated Th17 cells of healthy patients. This novel approach, and the data that ensued from it, with functional validation will illuminate inflammatory markers to target for creation of an immunotherapy for diseases plagued with inflammatory Th17 cells. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)