Immune-mediated inflammatory diseases (IMIDs) are a group of medical conditions affecting multiple organs. One such disease is inflammatory bowel disease (IBD). IMIDs are characterized by a dysregulated immune response and non-healing tissue damage, which promote a vicious cycle leading to chronic disease. Moreover, chronic inflammation can promote the development of cancer. IMIDs are among the leading causes of mortality in developed countries, and their prevalence is increasing. However, current therapies are predominantly based on the use of immune-suppressive drugs, are palliative in character, and do not offer a cure. They also have severe side effects, such as enhanced susceptibility to infections. Thus, there is a major need for new therapies. Therefore, the aim of our project is to build the basis for future therapies for inflammatory diseases and cancer.
A physiological tissue regeneration depends on fine-tuned interaction between the immune system, the tissue, and the microbiota. However, the complex communication between these three components and the molecules that mediate it is unclear. Understanding this is fundamental to prevent and treat immune-mediated diseases and cancer. Interleukin-22 (IL-22) is one key orchestrator of this communication: It is produced by immune cells and by acting on intestinal epithelial cells, it modulates the composition of the microbiota and promotes tissue regeneration. However, IL-22 can also promote both chronic inflammation and cancer. Of note, there is an endogenous inhibitor of IL-22, namely IL-22 binding protein (IL-22BP), which blocks IL-22 activity.
Our objectives are to study IL-22 and IL-22BP producing immune cells in terms of: their location, their functional and molecular heterogeneity, their origin and fate; and the role of the microbiota in regulating them. To this end, we will use new transgenic and gnotobiotic mouse models, single cell RNA sequencing and human samples. We will start to study the IL-22 - IL-22BP axis, in order to understand how the complex interactions between the immune system, the tissue, and the microbiota leads to either physiological or pathological tissue regeneration. On the basis of these data, we aim to go beyond IL-22 – IL-22BP and to identify general mechanisms regulating inflammation and cancer. This will finally provide the basis for therapies controlling inflammation and tissue regeneration in a spatio-temporal manner.
