The intestinal tract harbours a high diversity of permanently associated microbes. Therefore, it can be assumed that evolutionary pressure on the maintenance of intestinal homeostasis, the balance between tolerance and defence, has been one of the major forces driving the phylogenetic development of the immune system as it is present in humans today. The mucosa has to provide fast and differentiated responses to invading pathogens; on the other hand, safety margins of tolerance must be guaranteed as overwhelming immune actions against commensals and their associated molecular cues would similarly be as deadly as failing defences.
We are interested in a group of incurable diseases: human inflammatory bowel disease (IBD) with its two main subentities Crohn´s disease and Ulcerative colitis, where this delicate intestinal homeostasis is permanently disturbed.
A large number of genetic risk loci has been identified for IBD, with many of the affected genes pointing towards a crucial role of the intestinal epithelium and its capacity to control the symbiotic interaction with the gut microbiome. Yet the exact functional role of most of these genes still needs to be defined.
We are focusing on epithelial immune receptors such as the IBD susceptibility gene NOD2, autophagy involving gene ATG16L1 (linked to antimicrobial peptide secretion in IECs) and epithelial adsorptive pathways (BOAT1/ACE2). We try to answer the question of how the associated pathways are involved in licensing the colonisation and/or continuous host-microbe crosstalk under physiological conditions and how deleterious genetic variants may lead to increased susceptibility to inflammatory bowel disease.
We have shown that, in principle, many of these pathways are highly conserved, and have recently worked on the crosstalk between specific symbiotic bacteria, epithelial organ development and immune priming in marine invertebrates as new disease models for IBD.
On the technological side, we are developing sequencing and analysis methods to depict functional genomic changes on both the host and microbe side.
Jacqueline Moltzau Anderson