In vivo function of the activating NK cell receptors in intestinal inflammation (360G-Wellcome-203948_Z_16_A)

Chronic inflammation of the intestine leads to mucosal damage and manifests in inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn’s disease. Sustained inflammation can lead to transformation of cells, making IBD a major risk factor for colorectal cancer (CRC). The mechanisms involved in disease development and progression are still poorly understood. We study the interaction between immune cells, the gut microbiota and cells lining the inside of the intestine to understand the link between the immune system and the environment in the gut. Specifically, we focus on natural killer (NK) cells, which can recognise and kill malignant or infected cells that express certain stress signals. We hypothesise that under certain circumstances, this system is out of balance, leading to mucosal damage and chronic inflammation. We aim to dissect the mechanisms underlying the contribution of activating NK receptors in chronic inflammation of the gut epithelium and subsequent tumour development. To that end, we will investigate the interplay between the NK receptor expressing immune cells, inflammatory local responses and the gut microbiota using mice that lack certain NK cell receptors.