O-GlcNAc Transferase Suppresses Inflammation and Necroptosis by Targeting Receptor-Interacting Serine/Threonine-Protein Kinase 3 (Immunity)

The role of individual glucose metabolic pathways in innate immunity remains largely unknown. Li et al. demonstrate that attenuated O-linked ?-N-acetylglucosamine (O-GlcNAc) signaling enhances TLR-induced innate immune response and necroptosis. Mechanistically, O-GlcNAcylation of the kinase RIPK3 blocks RHIM-domain-mediated protein interaction and downstream signaling activation.