Dysregulation of T cell receptor N-glycosylation: A molecular mechanism involved in ulcerative colitis

• Autor(a) principal: Dias, A
• Data de Publicação: 2014
• Outros Autores: Dourado, J, Lago, P, Cabral, J, Marcos-Pinto, R, Salgueiro, P, Almeida, CR, Carvalho, S, Fonseca, S, Lima, M, Vilanova, M, Dinis-Ribeiro, M, Reis, CA, Pinho, SS
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://repositorio-aberto.up.pt/handle/10216/118211
• topic: Adult; Aged; Aged, 80 and over; Colitis, Ulcerative/genetics; Colitis, Ulcerative/metabolism; Female; Glycosylation; Humans; Male; Middle Aged; N-Acetylglucosaminyltransferases/genetics; N-Acetylglucosaminyltransferases/metabolism; Receptors, Antigen, T-Cell/metabolism; T-Lymphocytes/metabolism

The incidence of inflammatory bowel disease is increasing worldwide and the underlying molecular mechanisms are far from being fully elucidated. Herein, we evaluated the role of N-glycosylation dysregulation in T cells as a key mechanism in the ulcerative colitis (UC) pathogenesis. The evaluation of the branched N-glycosylation levelsandprofile of intestinalTcell receptor (TCR)wereassessedin colonic biopsies fromUCpatientsand healthy controls. Expression alterations of the glycosyltransferase gene MGAT5 were also evaluated. We demonstrated thatUCpatients exhibit a dysregulation ofTCRbranchedN-glycosylationonlamina propriaTlymphocytes. Patients with severe UC showed the most pronounced defect on N-glycan branching in T cells. Moreover, UC patients showed a significant reduction of MGAT5 gene transcription in T lymphocytes. In this study, we disclose for the first time that a deficiency in branched N-glycosylation on TCR due to a reduced MGAT5 gene expression is a new molecular mechanism underlying UC pathogenesis, being a potential novel biomarker with promising clinical and therapeutic applications.