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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

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

Journal

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

Vol. 115

ISSN: 0027-8424

Publisher: National Academy of Sciences

Indexing

ISI Web of Knowledge - 68 Citations

Scopus - 72 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10