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

• Autor(a) principal: Dias, A.
• Data de Publicação: 2018
• Outros Autores: 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.i, Lima, Margarida, Pedroto, I., Marcos-Pinto, Ricardo, Lago, P., Reis, C., Vilanova, M., Pinho, 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/10400.16/2316
• 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.