C.M. van Drunen

There is a growing awareness that the initiation of the immune response by inflammatory cells takes place with the context of the local mucosal surface. All signals derived from
the environment or from local tissue, are integrated, ultimately defining the immune response. This also implies that the airway epithelium is an active component of our immune system. Within the ENT department we study this process in relation the common pathologies of allergy and chronic rhinosinusitis. The most important lesson that came from our investigations is that, in order to understand our diseases better, we also need to understand the mechanisms that keep us healthy.

Allergy

We have shown that at birth the local immune system is immature and that this is characterized by local production of IL10.  Furthermore, the level of this regulatory
cytokine in epithelial cells and endothelial cells is directly correlated with the level of symptoms in allergic individuals. Moreover,  airway epithelium in allergic individuals is in an constant activated state, as it is not able to stop responding to innocent environmental triggers. This has consequences for inflammatory cells that link the innate to the adaptive immune response (dendritic cells and innate lymphoid cells) as well as effector
inflammatory cells

Chronic rhinosinusitis

Chronic rhinosinusitis is a common inflammatory disease of the nasal mucosa that strongly impacts on the life of patients. The pathogenesis of the disease is unknown, but is associated with diverse co-morbidities, including asthma. Using diverse approaches we study underlying pathological mechanisms focusing on the role of micro-organisms and the role of epithelium-fibroblast interactions.

The role of airway epithelium in keeping us healthy

In order to better study the active role of the mucosal immune system in keeping us healthy we have developed in vitro model that faithfully replicates the ultrastructural organization of our nose, including differentiated epithelial cells and cell from the adaptive immune system. Using stem cell technology and the abilities to introduce specific gene mutants with the CRISPR-CAS system we are studying the interaction of the immune system with local microbiota, the way influenza virus evolution is shaped, why Human Papilloma Virus induces disease in some individuals but not in others, and help define biomarkers that may aid in the diagnosis and the treatment of our diseases.