Autor(es):
Dias, A ; 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
Data: 2014
Origem: Repositório Aberto da Universidade do Porto
Assunto(s): 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
Descrição
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.
