Presenting Author: Naveena S Ujagar
, Graduate Researcher at Univ. of California, Irvine
Abstract:
Around 90% of the 537 million global diabetic adults suffer from type 2 diabetes (T2D), a metabolic disorder marked by heightened blood glucose due to insulin resistance or inadequate insulin production. T2D onset involves chronic systemic inflammation, predominantly influenced by T-helper 17 (Th17) cells. In T2D patients, defective fatty acid metabolic pathways contribute to Th17-driven inflammation. While lipid metabolism's role is established in in vitro Th17 cells, in vivo differentiated Th17 cells remain underexplored due to their low abundance. We addressed this challenge with a novel Th17 cell enrichment assay, capturing CD4+ T cells and magnetically purifying them based on IL-17A/17F/21 secretion for scRNAseq. From this transcriptomic data we established that the subsets of Th17 cells found in mice - pathogenic and non-pathogenic, are also present in humans, and that in vivo differentiated Th17 cells have a unique lipid metabolic phenotype from in vitro differentiated Th17 cells. We also characterized the metabolic state of these Th17 cells by utilizing the metabolic modeling algorithm Compass. Overlaying scRNAseq data from diabetic and control patients, we identified key lipid pathways driving Th17 inflammation in T2D. This pioneering study on endogenous Th17 cells in healthy and T2D patients, coupled with functional validation, unveils potential targets for developing immunotherapy for T2D.
Metabolism of Inflammatory T helper 17 cells from Type 2 Diabetic Patients
Category
Poster and Podium (Block Symposium)
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Date: May 6 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1