title: Dysregulation of T cell receptor N-glycosylation: a molecular mechanism involved in ulcerative colitis.
abstract: 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 levels and profile of intestinal T cell receptor (TCR) were assessed in colonic biopsies from UC patients and healthy controls. Expression alterations of the glycosyltransferase gene MGAT5 were also evaluated. We demonstrated that UC patients exhibit a dysregulation of TCR branched N-glycosylation on lamina propria T lymphocytes. 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.
authors: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors: Ana M
authors: AM
authors: Dias
authors: Joana
authors: J
authors: Dourado
authors: Paula
authors: P
authors: Lago
authors: Joana
authors: J
authors: Cabral
authors: Ricardo
authors: R
authors: Marcos-Pinto
authors: Paulo
authors: P
authors: Salgueiro
authors: Catarina R
authors: CR
authors: Almeida
authors: Sandra
authors: S
authors: Carvalho
authors: Sónia
authors: S
authors: Fonseca
authors: Margarida
authors: M
authors: Lima
authors: Manuel
authors: M
authors: Vilanova
authors: Mário
authors: M
authors: Dinis-Ribeiro
authors: Celso A
authors: CA
authors: Reis
authors: Salomé S
authors: SS
authors: Pinho
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D017351:N-Acetylglucosaminyltransferases