Asthma is a chronic inflammatory airway disease that affects around 334 million individuals worldwide and has a significant economic burden. Patients with severe asthma have persistent respiratory symptoms, reduced quality of life and frequent exacerbations, which require treatments with oral corticosteroids, hospitalization and may even be fatal. Despite important breakthroughs in the treatment of severe asthma, there is an unmet medical need to predict which patient is at risk of future exacerbations and who will respond well to the novel, but expensive biologic therapies. In response to external triggers (e.g. viral infections or exposure to air pollutants), inflammatory cells migrate from the blood to the airways. This process is facilitated by the interaction between cell adhesion molecules (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]) and integrins, but can be inhibited by the homeostatic protein “developmental endothelial locus-1” (DEL-1). In this project we will use a translational approach, in which we will combine analyses on human samples from asthma patients and controls, with in vitro experiments on human bronchial epithelial cells and mechanistic studies in a murine asthma model to unravel the importance of DEL-1 and cell adhesion molecules in severe asthma and to identify whether they can serve as biomarkers to predict treatment response to biologics.