Glycans as novel immunomodulators in inflammatory bowel disease

Portuguese scientists assessed whether glycosylation of T cells is a previously uncovered factor that tips the balance between homeostasis and intestinal inflammation. They proposed glycans as novel immunomodulators in inflammatory bowel disease (IBD), disclosing a promising predictive glycobiomarker associated with therapy response [1].

Ulcerative colitis patients exhibit a deficiency in branched glycosylation in intestinal T cells, which is reflective of disease severity. The Portuguese group tested the impact of specific glycans as immunomodulatory agents in vitro, ex vivo, and in preclinical mouse models of IBD, after which they performed clinical validation in human samples. Metabolic supplementation of ex vivo mucosal T cells from active ulcerative colitis patients with GlcNAc resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the Th1/Th17 immune response, and controlled T cell activity. Mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5−/−, MGAT5+/−) exhibited increased susceptibility to severe forms of colitis and early-onset disease. The treatment of these mice with glycan N-acetylglucosamine (GlcNAc) significantly reduced disease severity and suppressed disease progression; this was due to a controlled T cell-mediated immune response at the intestinal mucosa. Furthermore, the levels of expression of branched N-glycans analysed in colonic biopsies of ulcerative colitis patients close to diagnosis were found to predict failure to standard therapy.

1. Dias A. ECCO 2019, OP04.

Posted on 9 May, 20199 April, 2024