Project
Functional properties of sensory nerves and neuro-endocrine cells in airway hyper-reactivity
Rhinitis is a common disease characterized by mucosal irritation, excessive nasal secretions and congestion, leading to reduced life quality and substantial economic burden. Previously, we showed that in animal models and in rhinitis patients the sensory innervation hyper-reacts to noxious chemicals stimulating Transient Receptor Potential (TRP) cation channels. Furthermore, we found in clinical trials that targeting the sensory innervation via capsaicin-induced de-functionalization or histamine receptor antagonism significantly relieved symptoms in rhinitis patients. This clearly demonstrates the translational significance of our preclinical findings. These therapies are however limited, mainly due to a lack of understanding of how sensory neurons become hyper-reactive to airborne contaminants, food components, temperature changes and microbiome-produced chemicals. In this project we will use a translational approach and state-of-the-art methods to unravel cellular and molecular mechanisms underlying nociceptor sensitization. In particular, we will investigate the hypothesis that nasal hyper-reactivity arises from aberrant regulation of sensory Transient Receptor Potential channels in airway neuroendocrine cells and sensory neurons. The final outcome of this project will enhance our understanding of the underlying pathophysiology of neural hyper-reactivity, which may ultimately lead to a better clinical management of rhinitis.