Author(s):
Dias, Ana M. ; Correia, Alexandra ; Pereira, Márcia S. ; Almeida, Catarina R. ; Alves, Inês ; Pinto, Vanda ; Catarino, Telmo A. ; Mendes, Nuno ; Leander, Magdalena ; Oliva-Teles, MT ; Maia, Luís ; Delerue-Matos, Cristina ; Taniguchi, Naoyuki ; Lima, Margarida ; Pedroto, Isabel ; Marcos-Pinto, Ricardo ; Lago, Paula ; Reis, Celso A. ; Vilanova, Manuel ; Pinho, Salomé S.
Date: 2018
Persistent ID: http://hdl.handle.net/10400.22/14595
Origin: Repositório Científico do Instituto Politécnico do Porto
Subject(s): T lymphocytes; T cell receptor; Adaptive immune response; Branched N-glycosylation; Intestinal inflammation
Description
Mucosal 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.
