In the healthy organism, the immune sensing systems induce the appropriate type of inflammatory response to quickly and efficiently resolve infection and tissue damage. However, in many diseases, inflammation is inappropriate in terms of type, magnitude or duration. In this research section we will focus on sterile inflammation, a process that is primarily induced and maintained by innate immune sensing pathways, independent of microbial infection. Many sterile inflammatory conditions are due to the overproduction and tissue deposition of endogenous molecules, commonly referred to as damage associated molecular patterns, that are then sensed by the innate immune system. We have established several state-of-the-art animal models to cover various important sterile inflammatory conditions that are of particular interest to this Cluster and of great relevance from a medical stand-point. We favor model systems in which a genetic mutation causes a prototypical disease by disturbing a key biological process, which then results in the accumulation of a DAMP molecule. Even though these monogenetic sterile inflammatory conditions are very rare in the human system, the associated disease pathologies are usually highly informative on a mechanistic level and can generally be extrapolated to broader disease entities. Next to our reverse genetic approach in studying sterile inflammation in animal models, we will employ a phenotype-driven forward genetic approach in the human system to identify genetic components that play important roles in sterile inflammation. With our long-standing expertise in complex genetic disorders, we will address the role of genetic predisposition in DAMP-triggered inflammation. Furthermore, we plan to participate in a large clinical study initiative to investigate how physical and behavioral environmental factors modulate baseline inflammatory conditions in the healthy state.
1. Animal models of sterile inflammation.
2. Human model systems of sterile inflammation.
3. Environmental factors influencing the immune sensory system in healthy volunteers.