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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2018

Autores

Dias, AM (Autor) Outra; Alexandra Correia (Autor) FCUP; Pereira, MS (Autor) Outra; Almeida, CR (Autor) Outra; Alves, I (Autor) Outra; Pinto, V (Autor) Outra; Catarino, TA (Autor) Outra; Mendes, N (Autor) Outra; Leander, M (Autor) Outra; Oliva Teles, MT (Autor) Outra; Maia, L (Autor) Outra; Delerue Matos, C (Autor) Outra; Taniguchi, N (Autor) Outra; Lima, M (Autor) Outra; Pedroto, I (Autor) Outra; Marcos Pinto, R (Autor) Outra; Lago, P (Autor) Outra; Celso Reis (Autor) ICBAS; Manuel Vilanova (Autor) ICBAS; Pinho, SS (Autor) Outra

Revista

Título: Proceedings of the National Academy of Sciences of the United States of America

Vol. 115

ISSN: 0027-8424

Editora: National Academy of Sciences

Indexação

ISI Web of Knowledge - 68 Citações

Scopus - 72 Citações

Outras Informações

ID Authenticus: P-00P-ZE2

DOI: 10.1073/pnas.1720409115

Abstract (EN): 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10