Function of the intestinal immune system in health and disease
Immune mediated inflammatory diseases (IMIDs) are underpinned by inappropriately regulated immune responses. Proinflammatory responses to intestinal microbiota and microbial dysbiosis, for example, are characteristic of inflammatory bowel disease (IBD). Similarly, uncontrolled adaptive immune responses to gluten underlie celiac disease. In the Koning lab we aim to unravel the cellular basis for such IMIDs by in-depth analyses of the composition and function of immune system in health and disease. For this we combine single-cells mass cytometry, single-cell RNA-sequencing and flow cytometry with imaging mass cytometry to study the immune system in the affected organ. We combine this with functional studies to determine humoral and cellular mechanisms underlying these IMID. We anticipate that this will identify the nature of the disease-causative immune responses and the network of cellular interactions in which it causes chronicity in Immune Mediated Inflammatory Diseases.
Development of the human fetal immune system
Until recently the fetus was thought to be shielded from environmental factors. However, we have recently obtained evidence that there is extensive T cell memory formation in the fetal intestine, compatible with exposure to environmental antigen prior to birth. Interestingly, the process of memory formation is observed in both the conventional and regulatory CD4 T cell compartment, along with evidence for substantial additional cellular heterogeneity in both cell compartments, pointing towards a highly complex composition and likely associated functional heterogeneity of the immune system early in life. A major research effort is focused on the identification of the molecular and cellular mechanisms underlying this early development of the fetal immune system and to understand the potential ramifications thereof for immunity later in life.