ST2 (IL1RL1)

Class

IL-33/ST2 pathway inhibitor

ST2, also called IL1RL1, is the cell-surface receptor for interleukin-33 (IL-33), a signaling protein released by epithelial and endothelial cells when tissues are damaged or stressed. IL-33 acts as an 'alarmin' — an internal danger signal — that binds ST2 on immune cells such as mast cells, eosinophils, and group 2 innate lymphoid cells, triggering a cascade that promotes type 2 inflammation, the pattern of immune activity involving eosinophils, IgE, and mucus-producing cells. This pathway is a central driver of allergic and eosinophilic diseases, including asthma and chronic airway inflammation, and can be active even when classical allergic triggers such as allergen-specific IgE are absent. Because IL-33 sits upstream of multiple downstream type 2 mediators rather than one narrow effector, blocking ST2 has the potential to dampen a broad swath of inflammatory signaling at its source. Monoclonal antibodies directed against ST2 are designed to occupy the receptor and prevent IL-33 from engaging it, thereby interrupting this alarmin-driven inflammatory cascade. This approach is of particular interest in patients whose disease is not well explained by traditional allergic markers, since the alarmin pathway can operate independently of them.