P060. Immune unresponsiveness of human intestinal dendritic cells in ulcerative colitis is reversed by a novel bacterial peptide STp
H. Al-Hassi1, E. Mann1, D. Bernardo1, N. English1, S. Peake2, J. Landy2, R. Man2, A. Hart2, A. Stagg3, S. Knight1, 1Imperial College London, Immunology, London, United Kingdom, 2St Mark's Hospital, London, United Kingdom, 3Queen Mary University of London, London, United Kingdom
Gut dendritic cells (DC) maintain the balance between immunogenicity towards harmful pathogens and tolerance of commensal microbiota. Disruption of this balance can result in ulcerative colitis (UC). There is little information available regarding functions of gut DC in humans; we aimed to assess the function of human gut DC in UC and to condition these DC with a bacteria peptide (STp) secreted from L. plantarum that we recently demonstrated is found in the healthy human colon and has regulatory effects on gut DC.
Human DC from healthy controls and patients with active UC and inactive UC were isolated from colonic biopsies, conditioned for 24 hours +/− STp, and characterised by flow cytometry, immunohistochemistry and electron microscopy.
Expression of immature DC markers DC-SIGN and ILT-3 were increased on gut DC in UC. Expression of langerin (a molecule involved in phagocytosis), decreased in UC and DC-LAMP (DC maturation marker) expression was minimal and similar in both types of tissue. Immature phenotype was also confirmed by electron microscopy. Inactive UC gut DC exhibited a restricted stimulatory capacity for T-cells in mixed leukocytes reaction experiments but STp conditioning of DC restored their stimulatory capacity.
In the healthy gut, DC display specific tolerogenic properties and generate regulatory T-cells. The immature phenotype of DC observed in this study may account for the impairment of T cell activation and resulting in unresponsiveness. In addition data shown that this unresponsiveness could be systemic. It remains to be seen if this immune unresponsiveness by DC would lead to anergic T cells. However, DC function was partially restored by STp suggesting its role in gut homeostasis that is missing in UC. If such effects can be mirrored in vivo, potential implications are restoration of normal immune function in the gut in UC. Therapeutic applications include the use of STp as an additive and/or nutraceutical compound, leading a new era of probiotics and setting the basis for non-drug dietary therapy in IBD.