Research in our group is focused on unravelling the functions of lung dendritic cells, innate immune cells, and epithelial cells in asthma and respiratory viral infection.
Asthma is a chronic inflammatory disease of the airways characterized by eosinophilic airway inflammation, goblet cell metaplasia and bronchial hyperreactivity leading to sometimes irreversible airway obstruction and mucus plugging. A frequent cause of exacerbations is a respiratory viral infection. There is an epidemic of asthma in the Western world, of which the cause is unclear, and for which novel forms of prevention and treatment are urgently needed. In allergic asthma, allergen specific Th2 lymphocytes cause inflammation, as well as formation of allergen specific IgE, also known as allergic sensitization. In other forms of asthma, airway epithelial cells and innate type 2 immune cells control disease.
Our lab has found crucial roles for antigen presenting dendritic cells (DCs) in causing allergic sensitization at the inception of disease, and similarly described how DCs can exacerbate disease using models of relevant allergen exposure such as house dust mite (HDM), Alternaria and papain. Our studies showed that targeting airway DCs could be a novel therapeutic intervention strategy. Inhalation of allergens can only lead to asthma when airway epithelial cells are triggered through TLR4 and release endogenous danger signals such as ATP or uric acid and pro-Th2 innate cytokines like IL1, IL25, IL33, GM-CSF and TSLP. Moreover, we have shown that innate immune cells such as basophils or eosinophils would amplify Th2 responses initiated by DCs, via release of protein crystals made up from Charcot-Leyden crystal protein. Specified of particular environmental risk factors like cigarette smoke exposure and diesel exhaust particles promote HDM-driven asthma by triggering the function of DCs, epithelial cells or innate immune cells, whereas protective environments and a diverse microbiome promote tolerance to allergens.
The ultimate goal of our group is to find novel treatment strategies that alter the long-term course of asthma, which can prevent exacerbations and cure the disease.
Technology Transfer Potential
- Therapeutic targets in allergic asthma
- Mechanism of action of adjuvants
- Effector mechanisms of antibodies
This research is part of the VIB Grand Challenges Program. We specifically use our expertise in innate and adaptive immunity to improve the diagnosis and management of children with primary immunodeficiencies (PID) through the PID Grand Challenge Program. Since 2020 our group is also heavily involved in COVID-19 research and clinical trial design via the emergency COVID-19 VIB Grand Challenge Program.