PLX161115

GSE129829: Integrated Metabolomic and Transcriptomic Profiling Reveals Novel Activation Induced Metabolic networks in Human T cells

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Targeting metabolic pathways is emerging as an exciting new approach for modulating immune cell function and polarization states. Through carbon tracing and systems biology approaches that integrate metabolomic and transcriptomic profiling data we have identified important adaptations in human T cells metabolism which fuel their pro-inflammatory functions. We demonstrate that TCR stimulation leads to a significant increase in glucose and amino acid metabolism to fuel biosynthetic processes. Specifically, we demonstrate reprogramming of amino acid metabolism through increased expression of several enzymes such as CTPS1, IL4i1 and ASL. Furthermore, we demonstrate that cyclosporine represses these pathways providing novel insights into the immunosuppressive mechanisms of this drug. We translate our findings by demonstrating that the efficacy of conventional immunosuppressants can be increased upon combination with drugs that target metabolic pathways. Through these studies we provide a comprehensive resource for identification of metabolic targets which can be used to develop novel combinatorial regimens for treatment of intractable immune diseases. SOURCE: Shashank Jatav (shashank.jatav@elucidata.io) - Elucidata