Dias, A.Correia, A.Pereira, M.Almeida, C.Alves, I.Pinto, V.Catarino, T.Mendes, N.Leander, M.Oliva-Teles, M.Maia, L.Delerue-Matos, C.Taniguchi, N.iLima, MargaridaPedroto, I.Marcos-Pinto, RicardoLago, P.Reis, C.Vilanova, M.Pinho, S.2020-03-102020-03-102018-05-15Dias AM, Correia A, Pereira MS, et al. Metabolic control of T cell immune response through glycans in inflammatory bowel disease. Proc Natl Acad Sci U S A. 2018;115(20):E4651–E4660.0027-84241091-6490http://hdl.handle.net/10400.16/2316Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that 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. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.engT lymphocytesT cell receptoradaptive immune responsebranched N-glycosylationintestinal inflammationjournal article10.1073/pnas.1720409115