MIYISHI Eiji ≪Molecular Biochemistry and Clinical Investigation≫ “Core Fucosylation on T cells, Required for Activation of T-cell Receptor Signaling and Induction of Colitis in Mice, is Increased in Patients with Inflammatory Bowel Disease”
2016-03-07
PublishGastroenterology（2016） doi:10.1053/j.gastro.2016.03.002
Core fucosylation is one of the most important glycosylation involved in cancer and inflammation. The synthesis of core fucose is catalyzed by α1-6 fucosyltransferase (FUT8). In the present study, we investigated whether core fucosylation regulates T-cell activation and induction of colitis in mice, and is altered in patients with inflammatory bowel disease (IBD). Levels of core fucosylation were increased on T cells in both animal colitis models and IBD patients. Fut8－/－ mice developed less-severe colitis than Fut8+/+ mice due to decreases in T cell signaling. Adoptive transfer of Fut8－/－ T cells to RAG2-deficient mice also reduced the severity of colitis. TCR complexes formed on CD4+ T cells from Fut8－/－ mice did not signal properly following activation and were not transported to lipid rafts as a result from electron microscopy. Taken together, core fucosylation of the TCR is required for T-cell signaling and production of inflammatory cytokines, and induction of colitis in mice. Levels of TCR core fucosylation are increased on T cells from intestinal tissues of patients with IBD; this process might be blocked as a therapeutic strategy.
