The crosstalks between immune cells, bacteria and epithelial cells in the intestine: elucidating their cellular and molecular mechanisms

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The human gut is a complex organ whose proper function has major implications for health and disease of the entire body. There are three main compartments in the gut: (1) the immune system, whose main function is to protect from infections; (2) the epithelial layer, which similarly to the skin forms a barrier between our cells and the outside environment; (3) and the microbiota, which is the collection of multiple bacteria, viruses, fungi and parasites that live in our gut (for example, there are approximately as many bacteria in our gut as cells in the human body). Inappropriate interactions between these elements can influence the development of various diseases such as inflammatory bowel disease (IBD), diabetes, obesity and cancer, which constitute a significant public health and economic problem. IBD alone, which is the less prominent of these diseases, affects 620,000 people in the UK (Natalie et al., Gastroenterology 2012) and costs the NHS approximately £720 million a year. Thus, it is essential to understand how the immune cells, the epithelial cells and the gut microbiota interact in order to promote health and ameliorate and potentially treat disease. With this research programme, we aim to characterize how these 3 gut components interact. We are interested in studying a type of white blood cells called innate lymphoid cells (ILCs), which have important functions in the gut. These cells can be protective against infections, but can also promote inflammation. We want to discover which molecules are important in the communication between the intestinal epithelium, the innate lymphoid cells and the gut bacteria. These new molecules could them be used as targets to prevent/treat/cure intestinal inflammation.To identify these key molecules we developed a novel 'in vitro' system to culture white blood cells together with intestinal epithelial cells (from both mouse and human origins) and with specific bacteria. These 3D cultures of mini-guts in a dish will allow us to study the interactions between these three components as they occur in the gut.This research programme is going to be developed at King's College London, a UK leading university where we have all the research tools and support to be able to successfully complete it.As proper interactions between immune cells, epithelial cells and bacteria in the gut are critical for health, the results from these studies could lead to the improvement of patient's quality of life due to their potential impact on prevention and/or treatment of intestinal-associated diseases, such as IBD, diabetes, obesity and cancer.