EX-VIVO 3D MODEL OF T2-ASTHMA AND THE EFFECTS OF DUPILUMAB

Asthma is a complex condition with a multifaceted etiology that is not fully understood. Several endotypes have been identified in asthmatic pathology. The most common endotype is severe Type 2 asthma, which is characterized by Th2 lymphocyte polarization mediated by dendritic cells. This activation causes the induction of the inflammatory cytokine cascade, which is keyed by IL-4, IL-5, and IL-13. Several effects are induced by the cytokine-mediated inflammatory action, including the hyperplasia of goblet cells, the loss of barrier function, the excessive deposition of subepithelial collagen, the proliferation of myofibroblasts, the hyperplasia of airway smooth muscle, mucus secretion, airway hyper-reactivity, and tissue remodeling.This research seeks to study the inflammatory pathway characteristic of Th2 severe asthma on a culture model that is innovative in that it combines the immune component with a three-dimensional culture model. Th2 lymphocytes initiate the inflammatory process, and thus it is possible to obtain a co-culture model that mimics ex vivo the pathological conditions present in vivo. A model of this kind therefore represents an indispensable component of the second phase of the study, which is concerned with the assessment of the impact of the monoclonal antibody dupilumab, which acts by inhibiting the activity of the key cytokines involved in this pathological process, namely IL-4 and IL-13. This approach, which is characterised by an interdisciplinary perspective, makes a significant contribution to our understanding of asthma pathophysiology and underscores the potential of targeted therapies to transform the landscape of asthma treatment.