A colitis-associated glycome on CD4⁺ T cells

The repertoire of glycan structures on a cell surface (known as the glycome) is determined by glycan-modifying enzymes. Here, the authors show that memory CD4⁺ T cells in the inflamed intestines of mice with colitis have a unique colitis-associated glycome, characterized by the binding of galectin 4, that is associated with downregulation of the enzyme C2GNT (core 2 GlcNAc transferase). CD4⁺ T cells from the inflamed colon of patients with ulcerative colitis also had increased galectin 4 binding and decreased C2GNT expression. CD4⁺ T cells with restored expression of C2GNT were less able to induce colitis, consistent with their lack of the colitis-associated glycome. The colitis-associated glycome was shown to increase the proliferation of memory CD4⁺ T cells through galectin 4-mediated stabilization of lipid rafts, which resulted in sustained PKCθ activation downstream of immune synapses.