Targeting Interleukin-33/ST2 Pathway for the Treatment of Asthma

Inflammatory chronic illness of the airways, asthma affects more than 300 million individuals around the world currently. Airway hyperresponsiveness (AHR), inflammation, and remodeling are its defining features. The most common phenotype of asthma is allergic asthma. It is distinguished by a Th2-type inflammation, mast cell involvement, and allergen-specific IgE production. Finding a target that is a primary driver of immunologic activity is the aim of creating disease-modifying biotherapeutics for complicated diseases like asthma. Such a molecule seems to be interleukin (IL)-33, which is one of the first signalling molecules to be generated after epithelial injury and may coordinate the activation and recruitment of disease-causing cells. Uncontrolled IL-33 activity causes a variety of pro-inflammatory cells to become activated, which then increases the production of cytokines and chemokines that characterize the disease. Anti-ST2 receptor antibodies are one kind of treatment strategy that prevents IL-33 from binding to its receptor (ST2). Blocking the IL-33/ST2 pathway by anti-ST2 monoclonal antibody (Astegolimab) is efficient in controlling chronic lung inflammation, tissue remodelling and improving the responsiveness to steroid.

To Assess the ability of Astegolimab downstream pathway of ST2 using IL-33-stimulated lung epithelial cells and lung fibroblasts will be used. In addition, we will establish chronic asthma mouse model using OVA with IL-33 to evaluate the treatment ability of Astegolimab. The treatment with Astegolimab expect to: Attenuate the pro-inflammatory cytokines and inhibit the recruitment of inflammatory cells to the lung tissues to suppress lung inflammation, remodeling as well as improving responsiveness to steroid.