Metabolic control of T cell immune response through glycans in inflammatory bowel disease

• Autor(a) principal: Dias, Ana M.
• Data de Publicação: 2018
• Outros Autores: 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.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.22/14595
• topic: T lymphocytes; T cell receptor; Adaptive immune response; Branched N-glycosylation; Intestinal inflammation

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.