OP04 Turning sweet in inflammatory bowel disease: glycans as novel immunomodulators of T-cell-mediated immune response
A. Dias1, M. Pereira1, A. Correia1, I. Alves1, V. Pinto1, L. Azevedo2, L. Maia3, R. Marcos-Pinto3, M. Vilanova1, P. Lago3, S. Pinho*1
1Institute for Research and Innovation in Health (i3S), Immunology, Cancer and GlycoMedicine, Porto, Portugal, 2Medical Faculty, Department of Community Medicine, Information and Health Decision Sciences, Porto, Portugal, 3Porto Centre Hospital, Gastroenterology, Porto, Portugal
Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycans that was associated with disease severity.1,2 However, whether this altered glycosylation pathway shapes the course of the T-cell response constituting a targeted-specific mechanism in UC remains largely unknown. Moreover, the predictive capacity of this colonic glycosignature in terms of disease course and therapy response was investigated.
We used a multi-disciplinary approach that gathers in vitro, ex vivo, mouse models of disease and clinical validation in human samples. Human ex vivo CD3+ T cells (from intestinal lamina propria) were purified from fresh colonic biopsies and blood of 75 UC patients with active disease and with different Mayo endoscopic subscores. T cells were cultured and supplemented with increasing doses of the simple glycan
We demonstrated that metabolic supplementation of
We propose glycans as novel immunomodulators in IBD, further disclosing a promising predictive glycobiomarker associated with therapy response.
Note: This work was sponsored by ECCO grant 2017.
1. Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications.
2. Dias AM, Dourado J, Lago P,
3. Dias AM, Correia A, Pereira MS,
4. Pereira MS, Maia L, Azevedo LF,