Grant: Project Grant

Inflammatory bowel disease (IBD: mainly Crohn's disease and ulcerative colitis) is a life-long condition that affects around 325,000 Canadians. Characterised by periods of active disease and remission, the individual suffers with abdominal pain and chronic diarrhea, multiple hospitalisations (and surgeries) and co-morbidities, including anxiety and depression: the loss of quality-of-life is substantial (and in their caregiver(s) too). Currently there is no cure for IBD and while treatments have advanced considerably in the last decade, the best medications are effective in about 50% of individuals. Surely, we can do better. We present a research plan that uses knowledge of the human immune system with the goal to develop a new therapeutic approach to IBD, one that uses the individuals own immune cells. Macrophages are specialised immune cells that can promote repair to damaged tissue. In proof-of-concept studies, we discovered that human macrophages treated with the natural immune signal, interleukin (IL)-4 (cells designated as M(IL4)), reduce the severity of disease in pre-clinical models of colitis. We will test the hypothesis that factors in an inflamed gut reinforce or stabilise the M(IL4) phenotype to enhance or prolong its' anti-inflammatory, pro-healing activity, and the individual's period of disease remission. We propose to advance knowledge of the pro-healing activity of the human M(IL4) by exposing it to factors it would experience in an inflamed gut (i.e., IL-6, extracellular matrix, gut bacteria) to determine if this boosts or blunts its' anti-colitic effect: our preliminary data suggest the former. We seek to translate this discovery research that advances knowledge of the pro-healing function of the human M(IL4) into a new autologous cell therapy, whereby M(IL4) differentiated from blood immune cells of an individual with IBD are cryopreserved and given back to that individual when they experience a relapse in disease.