Rxivist logo

Elevated O-GlcNAcylation Enhances Pro-Inflammatory Th17 Function by Altering the Lipid Microenvironment

By Miranda Machacek, Zhen Zhang, Ee Phie Tan, Jibiao Li, Tiangang Li, Maria T Villar, Antonio Artigues, Todd Lydic, Chad Slawson, Patrick Fields

Posted 20 Apr 2018
bioRxiv DOI: 10.1101/305722

Chronic, low-grade inflammation increases the risk of atherosclerosis, cancer, and autoimmunity in diseases like obesity and diabetes. Here, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine) are present in naive CD4+ T cells from a diet-induced obesity murine model, and elevation in O-GlcNAc leads to increased pro-inflammatory IL-17A production. Importantly, CD4+ T helper 17 (Th17) cells, which secrete IL-17A, are increased in obesity and contribute to the inflammatory milieu. We found increased binding of the Th17 master transcription factor, RORγt, at the IL-17 locus and significant alterations in the lipid microenvironment, leading to increased ligands capable of increasing RORγt transcriptional activity. Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl CoA carboxylase 1 (ACC1), is necessary for production of these RORγt activating ligands and is O-GlcNAcylated. Thus, we have identified O-GlcNAc as a critical link between excess nutrients and pathological inflammation.

Download data

  • Downloaded 434 times
  • Download rankings, all-time:
    • Site-wide: 88,501
    • In immunology: 2,724
  • Year to date:
    • Site-wide: 123,385
  • Since beginning of last month:
    • Site-wide: 161,192

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


PanLingua

News