TRIFID · Training and Research in the Fundamentals of Inflammatory Disease

Final Activity Report Summary - TRIFID (Training and research in the fundamentals of inflammatory disease)

Chronic inflammatory disease affects almost one third of the European Union population and this figure is rising. Diseases that fall into this category range from allergic diseases like asthma to severe non-allergic autoimmune diseases, such as inflammatory bowel disease and rheumatoid arthritis, and also include chronic fibrotic diseases such as liver cirrhosis, lung fibrosis and renal disease. Few current therapies for chronic inflammatory diseases are effective and even though some may control the disease, they do not provide a cure. This project was based on the idea that an in depth understanding of the generic mechanisms that underlie chronic inflammation was needed in order to develop effective novel therapeutic interventions and improve prognosis for patients suffering from these diseases in Europe. The project thus set out to identify generic mechanisms involved in chronic inflammation in a variety of body tissues. Chronic inflammatory diseases have in common that they often start with an acute inflammatory response that later extends into a persistent phase. The novel and innovative approach of TRIFID was that the training and research carried out in the project concentrated on processes common to the development of chronic inflammation in different diseases. TRIFID was based at Birmingham University, a centre of excellence for inflammation research, with collaborative exchanges with five other centres in Europe whose model systems and technologies complemented the research and training available at Birmingham. The project recruited seven fellows: one did 9.5 months, two did a one year fellowship and then a follow on three year fellowship, and four did three year fellowships. The exchange visit for the three year fellows were carried out in world class institutes in Holland, Germany, Finland and Switzerland and these resulted in extended collaborations. The fellows received multidisciplinary training in skills that could not be offered by the coordinating centre alone. The primary aim of this project was to produce a group of young scientists in the European Union with state of the art training in inflammation biology, who through their time as a Marie Curie fellows would have gained an appreciation of the complexity of chronic inflammation and acquired skills and personal contacts that would ensure they could make a significant contribution to research in this area at international level in the future. Of the three one year fellows, two went on to study for a PhD as part of the Marie Curie scheme by doing a three year fellowship. Of the three year fellows, all six registered for a PhD and four had been awarded their PhD by the time of the project completion. The other two were preparing their thesis at the same time. Three of these fellows had already secured postdoctoral fellowships in the area of inflammation, one stayed on in the United Kingdom, one returned to her home country and one moved to Spain. The project thus delivered young researchers with a commitment to inflammation research and with increased mobility. For research, the focus was on three elements of chronic inflammation, namely recruitment, survival and retention of inflammatory cells at inflamed sites. For cell recruitment highly novel data was produced showing that neutrophils were able to transmigrate, i.e. re-enter the blood, after being recruited from blood, though the significance of the findings for inflammation remained to be determined. With respect to the mechanisms that allowed cells to be directed to specific inflamed tissues, the research showed a clear role for the adhesion molecule MadCam1 and the chemokine CCL25 in directing cells to the gut and liver. These molecules represented novel drug targets in inflammatory diseases such as inflammatory bowel disease (IBD). In the area of cell survival significant the role of fibroblasts, previously thought to mainly play a structural role within tissues, in setting up networks between immune cells was revealed, with fibroblasts interacting with T lymphocytes to generate survival signals for neutrophils, thus contributing to the persistence of these destructive cells at inflamed sites. The third major area of progress was in identifying a key role for the cytokine IL6 in regulating the switch from acute to chronic inflammation in both the eye and joint.

Data: CORDIS, © European Union