DOP081 Glycosylation of T cells: a novel targeted-specific therapeutic strategy in IBD
Dias A.M.*1,2, Correia A.3, Pereira M.1, Almeida C.R.4, Alves I.1, Lima M.5,6, Marcos-Pinto R.2,7,8, Reis C.A.1,2,9, Vilanova M.2,3, Lago P.8, Pinho S.S.1,9
1Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) & i3S – Instituto de Investigação e Inovação em Saúde, Glycobiology in Cancer, Porto, Portugal 2Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal 3Instituto de Investigação e Inovação em Saude (I3S)/Institute for Molecular and Cell Biology (IBMC), Immunobiology Group, Porto, Portugal 4Instituto de Investigação e Inovação em Saude (I3S)/ Institute of Biomedical Engineering (INEB), NEWTherapies Group, University of Porto, Porto, Portugal 5Centro Hospitalar do Porto, Multidisciplinary Unit for Biomedical Research (UMIB), Porto, Portugal 6Centro Hospitalar do Porto, Hematology Department, Porto, Portugal 7Medical Faculty, Centre for Research in HealthTechnologies and Information Systems (CINTESIS), Porto, Portugal 8Centro Hospitalar do Porto, Department of Gastroenterology, Porto, Portugal 9University of Porto, Medical Faculty, Porto, Portugal
The incidence of Inflammatory bowel disease (IBD) is increasing worldwide and the current therapeutic strategies are limited by reduced effectiveness, high costs, and/or presence of toxic/side effects. We have previously demonstrated that UC patients display a deficiency in the levels of glycosylation of mucosal T cells that was associated with disease severity .
However, it remains unknown whether this mechanism can be therapeutically targeted in IBD.
The results on
We observed that increasing doses of specific glycans resulted in a significant reduction of T cell proliferation, suppression of Th1 and Th17 response through decreasing the expression of the transcription factors, T-bet and RORγt and the respective cytokines production, TNF-α, INF-γ and IL17A. Downstream TCR signaling was also suppressed as observed by the reduction in phosphorylation levels of ZAP70 and LAT. Interestingly, our
Our data suggest that enhancing the glycosylation of T cells resulted in a significant suppression of T cell mediated-immune response associated with the control of intestinal inflammation and suppression of disease severity and progression. Glycans are thus a novel and promising target-specific immunomodulatory therapy in IBD.
 Dias, AM et al., (2014), Dysregulation of T cell receptor N-glycosylation: a molecular mechanism involved in ulcerative colitis, Human Molecular Genetics