Please use this identifier to cite or link to this item: https://repositorio-aberto.up.pt/handle/10216/118211
Author(s): 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
Title: Dysregulation of T cell receptor N-glycosylation: A molecular mechanism involved in ulcerative colitis
Publisher: Oxford University Press
Issue Date: 2014
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 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.
Subject: 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
URI: https://repositorio-aberto.up.pt/handle/10216/118211
Source: Human Molecular Genetics, vol.23(9), p. 2416-2427
Related Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/111358/PT
info:eu-repo/grantAgreement/FCT/COMPETE/125428/PT
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/124445/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F63094%2F2009/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F77386%2F2011/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

Files in This Item:
File SizeFormat 
Dysregulation of T cell receptor N glycosylation.pdf1.02 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.