Novel anti inflammatory cytokines and cell therapies for the treatment of inflammatory bowel disease

Inflammatory bowel disease is a chronic immune mediated disorder affecting the intestine with no known cure. The pathogenesis of this disease results from immune dysregulation and an imbalance between pro inflammatory cells and cytokines. IL37 is a novel anti-inflammatory cytokine which is reduced in the circulation of patients with auto-immune diseases, including inflammatory bowel disease. Human peripheral blood mononuclear cells are capable of producing IL37, and in particular the T cell subset. Aberrant helper T cell responses play a key role in the pathogenesis of IBD. Thus it is of paramount importance to understand the triggers for pro and anti-inflammatory cytokine production by T cell subsets of patients with inflammatory bowel disease. This project will first look at characterising IL37 production in different cell subsets in the blood and lamina propria of patients with inflammatory bowel disease. Concurrently, patient data on disease activity, medication use and response will be collected. Disease activity and response to currently available medications will be correlated with IL37 production to assess whether this cytokine plays a role not only in pathogenesis of disease, but also response to immunomodulating medications. Regulatory T cells (Tregs) are responsible for dampening down aberrant inflammation and control autoimmune disease. Tregs are dysfunctional in inflammatory bowel disease. The second part of this project will look at defining the ability of Treg to respond to and produce IL37 as a means of developing a highly novel cell based therapy.