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P050. Unravelling the immunomodulatory functions of glucagon like peptide-2 on dendritic cells

C.T. Tee1, D. Bernardo1, A.U. Murugananthan1, E.R. Mann1, S.T.C. Peake2, K. Wallis2, S.M. Gabe2, H.O. Al-Hassi1, S.C. Knight1

1Antigen Presentation Research Group, Imperial College, London, United Kingdom; 2St. Mark's Hospital, London, United Kingdom

Aims: Animal studies have shown that Glucagon Like Peptide-2 (GLP-2) can reduce mucosal inflammation; it decreases proinflammatory cytokines and ameliorates chronic colitis [1]. However, we do not yet know whether this anti-inflammatory effect occurs in humans. If so, it potentially opens the door for use of GLP-2 as a therapy in conditions like inflammatory bowel disease. Therefore we studied the immunomodulatory functions of GLP-2 in humans.

Methods: Dendritic cells (DC) enriched from human blood of healthy volunteers were cultured in-vitro for 24 hours with GLP-2 at concentrations of 1 pM, 1 nM and 1 μM. The effect of GLP-2 on DC survival was determined using apoptosis experiments. Phenotype and functions of DC were then assessed by flow cytometry and mixed leucocyte reaction (MLR) respectively. Each experiment was performed independently at least 3 times and analysed for statistically significant effects.

Results: Apoptosis experiments showed that GLP-2 at all concentrations did not have a toxic effect on DC; their survival after in-vitro culture with GLP-2 was similar to that in basal control culture (p = NS). GLP-2 conditioning changed the phenotype of DC with reduction in HLA-DR intensity (p = 0.0243) and increase in CD14 expression (p = 0.0237), compared with basal control culture. However, the down-regulation of HLA-DR intensity and up-regulation of CD14 expression did not correlate with an increase in the phagocytic capacity (p = NS). Other markers of immature DC, ILT3 and DC SIGN, were not affected. TLR2/4 expression was also not affected by the treatment (p = NS). Finally, MLR experiments showed that GLP-2 treatment on DC did not have an effect on their stimulation of T cell proliferation (p = NS).

Conclusion: GLP-2 reduced HLA-DR and increased CD14 on DCs, though this effect does not correlate with T-cell stimulation in-vitro. More studies are needed to detect any functional significance to the changes GLP-2 induced on dendritic cells.

1. Catherine P.A. Ivory, Laurie E. Wallace, Donna-Marie McCafferty, and David L. Sigalet (2008). ‘Interleukin-10-independent anti-inflammatory actions of glucagon-like peptide 2.’ Am J Physiol Gastrointest Liver Physiol 295: G1202-G1210.