Models of Dysbiosis to Investigate the Role of SOCS3 in Intestinal Inflammation

Suppressor of cytokine signalling 3 is an important protein in the maintenance and homeostasis of the intestinal epithelium. Its dysregulation is associated with severe disease including inflammatory bowel disease and colorectal cancer. It is therefore a tightly regulated protein, its oscillatory nature thought to be regulated by both transcriptional and post-translational mechanisms such as proteasomal degradation and autophagy. The intestinal microbiota has been implicated in intestinal inflammation, inflammatory bowel disease and inflammation-associated cancer. We used two models of dysbiosis in both human resection specimens and cultured human intestinal epithelial cells. Both models are used to investigate the impact of dysbiosis on inflammatory signalling pathways and autophagy. In addition, we used transgenic cells to investigate the impact of SOCS3 expression upon these pathways. Our results suggest that dysbiosis may stimulate autophagy, but not chronic inflammation. Meanwhile, SOCS3 modulation did not impact inflammatory signalling pathways, but may be playing a role in the modulation of autophagy