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”
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.